Circulating progesterone levels and ongoing pregnancy rates in controlled ovarian stimulation cycles for in vitro fertilization: analysis of over 4000 cycles

background: The influence of elevated serum progesterone levels during in vitro fertilization/intracytoplasmic sperm injection (IVF/ ICSI) cycles on pregnancy rates is a matter of continued debate among fertility clinicians. Efforts to resolve this question have been impeded by the various assays used to measure progesterone and the different, arbitrary threshold values for defining ‘high’ progesterone levels. methods: A non-interventional, retrospective, observational, single-centre cohort study evaluated the relationship between serum progesterone levels on the day of human chorionic gonadotrophin (hCG) administration and the ongoing pregnancy rate in 4032 patients undergoing IVF/ICSI cyc…

Cigarette smoking affects uterine receptiveness

Background Cigarette smoking has long been known to have an effect on female fertility. The existence of an ovarian factor is clear when one considers that the mean age of the menopause is lower and IVF cycle outcome is worse in heavy smokers. The hypothesis of a concomitant uterine effect is raised by indirect evidence from in vitro and in vivo studies, but as yet, no direct evidence has been gained to confirm its existence. In this work, we analyse the association between smoking habit in oocyte recipients and cycle outcome. Methods We have retrospectively analysed the outcome of all oocyte donation cycles performed in our clinic from January 2002 to June 2005 from which there was availab…

P20Early membrane funnelling may occur from 16 weeks onwards and carries a worse prognosis

Background Sonographic screening for cervical incompetence during pregnancy is currently a routine procedure. However, no consensus exists on the optimal gestational age to perform such screening. Method Serial transvaginal ultrasound examinations of the uterine cervix were routinely performed from 12 weeks onwards. The screening was considered positive when membrane funnelling was present or the cervical length was < 2 cm. Therapeutic measures included bed rest, antibiotics, tocolytic treatment and a modified McDonald's cervical suture (up to 25 weeks). Results Membrane funnelling was detected between 16 and 22 weeks (group A) in 9 women (31%); between 23 and 28 weeks (group B) in 11 women…

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…

El diagnóstico genético preimplantacional y sus nuevas indicaciones en reproducción asistida

Cumulative newborn rates increase with the total number of transferred embryos according to an analysis of 15,792 ovum donation cycles

Objective To measure the success of in vitro fertilization (IVF) of donated ova according to cumulative newborn rates (CNBR) per number of embryos required to achieve at least one newborn (EmbR), considering in addition the relevance of age and infertility etiology. Design Survival curves and Kaplan-Meier methods were employed to analyze CNBR with respect to the number of EmbR in a retrospective cohort of oocyte donation recipients. Setting University-affiliated infertility center. Patient(s) Infertile couples undergoing IVF with oocyte donation. Intervention(s) None. Main Outcome Measure(s) CNBR per EmbR. Result(s) The CNBR increased radically (up to 64.8%) between 1 and 5 EmbR, moderately…

Obesity and assisted reproductive technology outcomes.

Obesity is a rising health problem in Western societies. It has been related to increased morbidity and mortality rates due to several pathologies. In the field of gynaecology and reproduction, obesity is associated with menstrual disorders, hirsutism, infertility, miscarriage and obstetric complications. It is known to impair human reproduction through different mechanisms such as insulin resistance, hyperandrogenism and elevated leptin levels. Weight management and dietary intervention can reverse this situation and improve reproductive function. Obesity can also impair the outcome of assisted reproductive technologies. The lower probability of a healthy live birth described in obese wome…

Low-dose dopamine agonist administration blocks vascular endothelial growth factor (VEGF)-mediated vascular hyperpermeability without altering VEGF receptor 2-dependent luteal angiogenesis in a rat ovarian hyperstimulation model.

No specific treatment is available for ovarian hyperstimulation syndrome (OHSS), the most important complication in infertile women treated with gonadotropins. OHSS is caused by increased vascular permeability (VP) through ovarian hypersecretion of vascular endothelial growth factor (VEGF)activating VEGF receptor 2 (VEGFR-2). We previously demonstrated in an OHSS rodent model that increased VP was prevented by inactivating VEGFR-2 with a receptor antagonist(SU5416).However,duetoitstoxicity(thromboembolism) and disruption of VEGFR-2-dependent angiogenic processes critical for pregnancy, this kind of compound cannot be used clinically to prevent OHSS. Dopamine receptor 2 (Dp-r2) agonists, use…

Bed rest after embryo transfer negatively affects in vitro fertilization: a randomized controlled clinical trial.

Objective To evaluate the influence of 10 minutes of bed rest after ET on the achievement of a live-born infant (LBI) in patients undergoing IVF treatment with oocyte donation (OD). Design Prospective, randomized, parallel assignment, controlled trial. Setting Private IVF center. Patient(s) A total of 240 patients undergoing a first IVF cycle with OD in our center. Intervention(s) Ten minutes of bed rest after ET or no bed rest, that is, allowing patients to ambulate immediately after the ET. Main Outcome Measure(s) The primary outcome was LBI rate per randomized patient. Secondary outcomes were implantation rate and biochemical and clinical miscarriage rates. Result(s) LBI rates (56.7% vs.…

Cumulative live-birth rates per total number of embryos needed to reach newborn in consecutive in vitro fertilization (IVF) cycles: a new approach to measuring the likelihood of IVF success.

Objective To report the use of cumulative live-birth rates (CLBRs) per ovarian stimulation cycle to measure the success of IVF is proving to be the most accurate method for advising couples who failed to conceive, although the accuracy yielded is relatively low, and cycle outcome is highly dependent on the number of embryos replaced. Our aim with this work is to report the CLBRs of IVF as a function of the number of embryos required to reach a live birth (EmbR), considering age, day of ET, and infertility etiology. Design Survival curves and Kaplan-Meier methods to analyze CLBR in a retrospective cohort with respect to the number of EmbR. Setting University-affiliated infertility center. Pa…

EP08.12: Cavum veli interpositi: two cases and clues to differentiate it from a true brain midline cystic lesion

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

Clinical factors affecting endometrial receptiveness in oocyte donation cycles.

Objective To provide a summary of the actual knowledge about the clinical factors affecting the oocyte recipient (other than those associated with uterine cavity abnormalities) on the outcome of oocyte donation cycles. Design Review of the literature. Setting Information regarding the association between age, body mass index (BMI), endometrial priming, tobacco consumption, hydrosalpinx, and endometriosis/adenomyosis in oocyte recipients and the results of oocyte donation cycles. Result(s) Recipient age and the presence of hydrosalpinx are clearly associated with a poorer outcome in oocyte donation cycles. The negative impact of tobacco consumption has recently been confirmed. The exact rele…

Examination of the fetal brain by transabdominal three-dimensional ultrasound: potential for routine neurosonographic studies

Objective To evaluate the role of transabdominal three-dimensional (3D) ultrasound in the assessment of the fetal brain and its potential for routine neurosonographic studies. Methods We studied prospectively 202 consecutive fetuses between 16 and 24 weeks' gestation. A 3D ultrasound volume of the fetal head was acquired transabdominally. The entire brain anatomy was later analyzed using the multiplanar images by a sonologist who was expert in neonatal cranial sonography. The quality of the conventional planes obtained (coronal, sagittal and axial, at different levels) and the ability of the 3D multiplanar neuroscan to visualize properly the major anatomical structures of the brain were eva…

Human somatic cells subjected to genetic induction with six germ line-related factors display meiotic germ cell-like features

AbstractThe in vitro derivation of human germ cells has attracted interest in the last years, but their direct conversion from human somatic cells has not yet been reported. Here we tested the ability of human male somatic cells to directly convert into a meiotic germ cell-like phenotype by inducing them with a combination of selected key germ cell developmental factors. We started with a pool of 12 candidates that were reduced to 6, demonstrating that ectopic expression of the germ line-related genes PRDM1, PRDM14, LIN28A, DAZL, VASA and SYCP3 induced direct conversion of somatic cells (hFSK (46, XY) and hMSC (46, XY)) into a germ cell-like phenotype in vitro. Induced germ cell-like cells …

Embryo Aneuploidy Screening for Unexplained Recurrent Miscarriage: A Minireview

Problem:  The aim of this study was to investigate the incidence of chromosomal abnormalities in unexplained recurrent miscarriage (RM) patients and assess the role of pre-implantation genetic diagnosis (PGD) in preventing subsequent pregnancy loss and improving pregnancy outcome. Method of Study:  Pre-implantation genetic diagnosis was performed in 241 RM cycles and in 35 cycles in patients undergoing PGD for sex-linked diseases (control group). Chromosomes 13, 16, 18, 21, 22, X and Y were analysed by fluorescence in situ hybridization. Results:  The implantation and pregnancy rates in RM patients were 26.4 and 36.5% versus 20.6 and 29.0% in the control group, respectively. The percentage …

Additive effect of factors related to assisted conception on the reduction of maternal serum pregnancy-associated plasma protein A concentrations and the increased false-positive rates in first-trimester Down syndrome screening.

Objective To analyze whether assisted conceptions need adjustments in first-trimester Down syndrome screening and why modifications in screening markers occur. Design Eleven-year cohort retrospective analysis. Setting Maternal-fetal medicine unit. Patient(s) Two thousand eleven naturally conceived normal singleton pregnancies and 2,042 normal singleton pregnancies achieved with assisted conception: 350 by IUI and 1,692 with IVF (n = 328) or intracytoplasmic sperm injection (ICSI; n=1,364), using nondonor (n = 1,086) or donated ova (n = 606), with fresh (n = 1,432) or frozen (n = 260) embryos. Intervention(s) Comparison of ultrasound and biochemical markers of first-trimester Down syndrome s…

Analysis of chromosomal abnormalities in testicular and epididymal spermatozoa from azoospermic ICSI patients by fluorescence in-situ hybridization

BACKGROUND: An increased incidence of numerical chromosomal abnormalities has been reported in the ejaculated spermatozoa of infertile patients. However, there are few cytogenetic studies of testicular and epididymal spermatozoa, and their results are still controversial. METHODS: Fluorescence in-situ hybridization (FISH) analysis of chromosomes 13, 18, 21, X and Y was performed on seven testicular samples and two epididymal samples from patients with obstructive azoospermia (OA), and on 13 testicular samples from patients with non-obstructive azoospermia (NOA). Five ejaculated sperm samples from normozoospermic fertile donors were evaluated as a control group. RESULTS: Both epididymal sper…

P01.28: Analysis of nuchal translucency measurements in pregnancies achieved by assisted reproduction techniques

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…

EP07.12: Calcar avis: a normal cerebral anatomic structure that can also mimic parenchymal pathology

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.

OC2.01: Examination of the fetal brain by three-dimensional ultrasound: potential for routine neurosonographic studies

Objective: To evaluate the role of three-dimensional (3D) ultrasound in the assessment of the fetal brain and its potential for routine neurosonographic studies. Methods: We studied prospectively 202 consecutive brain fetuses between 16 and 24 weeks’ gestation. A 3D-ultrasound volume of the fetal head was acquired transabdominally. The entire brain anatomy was later analyzed by a sonologist expert in neonatal cranial sonography using the multiplanar images. The quality of the conventional planes obtained (coronal, sagittal and axial, at different levels) and the ability to visualize properly the major brain anatomic structures were evaluated. Results: Acceptable rendered cerebral volumes we…

Serum luteinizing hormone in patients undergoing ovarian stimulation with gonadotropin-releasing hormone antagonists and recombinant follicle-stimulating hormone and its relationship with cycle outcome.

The serum LH was determined on days 3, 6, and 8 of stimulation and on the day of hCG in 110 normogonadotropic patients undergoing controlled ovarian hyperstimulation (COH) for IVF induced with GnRH antagonists and recombinant FSH, creating three groups of patients according to Tukey's hinges (percentiles 25 and 75) for each determination. No differences were observed between the number of oocytes recovered or the fertilization, implantation, and pregnancy rates (PR) of the groups, although patients with high serum LH levels during stimulation showed significantly higher serum E2 levels on the day of hCG.

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…

Vitrification of human mature oocytes in clinical practice.

Oocyte cryopreservation has long been the focus of unsuccessful efforts to perfect its clinical application. Lately, vitrification has been shown to provide high degrees of success by different research groups. This review attempts to address the efficiency of oocyte vitrification in clinical practice through an analysis of reports of IVF cycles in which embryo transfers have been conducted with vitrified metaphase-II human oocytes.

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 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…

First trimester biochemical screening for Down's syndrome in singleton pregnancies conceived by assisted reproduction

BACKGROUND: Serum biochemical markers [free betahCG (fbetahCG); pregnancy-associated plasma protein-A (PAPP-A)] used in first trimester Down's syndrome screening have not been fully investigated in pregnancies achieved by assisted reproduction techniques. We present data on pregnancies conceived by all types of assisted reproduction techniques, including pregnancies following ovum donation (OD) and a large sample by ICSI. METHODS: First trimester Down's syndrome screening was performed in 1054 normal singleton pregnancies: natural conception (n = 498), ovulation induction (OS, n = 97), IVF (n = 47), ICSI (n = 222) and OD (n = 190). RESULTS: No differences in maternal levels of fbetahCG and …

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 …

Preimplantation genetic diagnosis by fluorescence in situ hybridization: clinical possibilities and pitfalls.

Preimplantation genetic diagnosis using the fluorescence in situ hybridization technique (FISH) is being used widely to prevent the transmission of sex-linked diseases, to screen for translocations, and for aneuploidy screenng in specific invitro fertilization (IVF) patient groups, along with FISH analysis of spematozoa in intertile men. In this study, we aim to critically analyze our clinical results in patients at risk of transmitting sex-linked diseases (n = 55), in carriers of translocations (n = 43), in women who have recurent miscarriage (two or more miscarriages) (n = 128), recurrent IVF failure (three or more failed IVF attempts) (n = 47), and patients of advanced maternal age (37 y…

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…

P01.46: The incidence and characteristics of first-trimester fetal lateral neck cysts

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…

Improved accuracy of hysteroembryoscopic biopsies for karyotyping early missed abortions

Abstract Objective To assess the potential of direct embryo and chorion biopsies obtained by hysteroembryoscopy for karyotyping early missed abortions. Design Clinical prospective descriptive study. Setting Instituto Valenciano de Infertilidad, Valencia, Spain. Patient(s) Sixty-eight women (71 gestational sacs) with missed abortions. The gestational age on ultrasound was 6.3 weeks (range, 4–10 weeks). Intervention(s) Transcervical hysteroembryoscopy before curettage. Main outcome measure(s) Comparison between the cytogenetic results from hysteroembryoscopic biospies and those of the curettage material. Result(s) Hysteroembryoscopic biopsies could be taken in 97.2% of the gestational sacs. D…

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…

FISH screening of aneuploidies in preimplantation embryos to improve IVF outcome

Preimplantation genetic diagnosis (PGD) has transformed the approach to the infertility patient in the IVF setting. Although the principal applications of PGD have been to prevent the transmission of sex-linked diseases, in time and with growing knowledge of the chromosomal abnormalities observed in preimplantation embryos, its applications have widened. Nowadays, apart from its implications in the prevention of transmission of chromosomal and genetic abnormalities, PGD is being used with increased frequency to improve the IVF outcome in patients with advanced maternal age (or =38 years of age), recurrent miscarriage (or =2 miscarriages), recurrent IVF failure (or =3 failed IVF attempts) an…

Machine Learning-Based Approach Highlights the Use of a Genomic Variant Profile for Precision Medicine in Ovarian Failure

Ovarian failure (OF) is a common cause of infertility usually diagnosed as idiopathic, with genetic causes accounting for 10–25% of cases. Whole-exome sequencing (WES) may enable identifying contributing genes and variant profiles to stratify the population into subtypes of OF. This study sought to identify a blood-based gene variant profile using accumulation of rare variants to promote precision medicine in fertility preservation programs. A case–control (n = 118, n = 32, respectively) WES study was performed in which only non-synonymous rare variants &lt

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 …

False positive rate of an arrayCGH platform for single-cell preimplantation genetic screening and subsequent clinical application on day-3

In this work, false positive rate of an arrayCGH platform for its use in day-3 single-blastomere analysis was calculated. For this purpose, 38 embryos diagnosed as abnormal on day-3 by FISH were re-biopsied on day-4. Single-cell day-4 arrayCGH diagnosis was then performed. A successful amplification was obtained in 97.4 % (37/38) of the day-4 cells analysed by arrayCGH. Day-3 FISH and day-4 arrayCGH diagnosis were concordant in 35/37 cases. The two discordant embryos were spread and all the cells from each embryo were re-analysed by FISH on day 5. The same error rate (2.7 %) for day-3 FISH and day-4 arrayCGH was obtained when comparing day-5 FISH re-analysis. After this pre-clinical phase, …

First-trimester diagnosis of thrombocytopenia-absent radius (TAR) syndrome in a triplet pregnancy

The use of long-acting forms of gonadotropin-releasing hormone analogs (GnRHa Depot) increase miscarriage rates in oocyte donation cycles.

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…

Oocyte vitrification versus ovarian cortex transplantation in fertility preservation for adult women undergoing gonadotoxic treatments: a prospective cohort study

Objective To compare the efficacy of oocyte vitrification (OV) with that of ovarian cortex cryopreservation and transplantation (OCT) in women undergoing gonadotoxic treatments. Design Prospective observational cohort study. Setting Not applicable. Patient(s) Candidates for chemo-/radiotherapy who joined our fertility preservation (FP) program were included in this study between 2005 and 2015. One cohort included 1,024 patients undergoing OV; the other cohort included 800 patients undergoing OCT. Intervention(s) OV using the cryotop device and OCT using a slow freezing protocol. Main Outcome Measure(s) Live-birth rate (LBR) and clinical pregnancy rate (CPR). Result(s) Basal antimullerian ho…

P-86

Impact of chromosomal abnormalities on preimplantation embryo development.

Objectives To evaluate the influence of numerical chromosomal abnormalities on preimplantation embryo development. Methods This study includes 6936 embryos from 1245 women undergoing preimplantation genetic diagnosis (PGD). Indications for aneuploidy screening were: recurrent miscarriages, implantation failure, severe male factor, advanced maternal age, and mixed causes. Embryo biopsy was performed on day 3, and embryos were co-cultured until day 5, when embryo transfer was performed. Results In the aneuploidy screening regimen, normal euploid embryos showed significantly higher blastocyst rates (68.2%) compared to chromosomally abnormal (42.8%, p < 0.0001) and mosaic (53.7%, p < 0.0001) em…

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…

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…

The role of thrombophilia and thyroid autoimmunity in unexplained infertility, implantation failure and recurrent spontaneous abortion.

The role of thrombophilia and thyroid autoimmunity in unexplained infertility (UI), implantation failure (IF) and recurrent spontaneous abortion (RSA) is controversial and poorly understood.From March, 2004 to January, 2007, 119 women were prospectively included: 32 oocyte donors, 31 patients with UI, 26 with IF and 30 with RSA. The IF and RSA groups presented normal preimplantation genetic screening. Protein C, protein S, antithrombin III, lupus anticoagulant, activated protein C resistance (APCR), immunoglobulin M and G anticardiolipin antibodies, homocystine, Factor V Leiden, prothrombin G20210A mutation, methylentetrahydrofolate reductase C677T mutation, thyroid-stimulating hormone (TSH…

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…

Fertilization after intracytoplasmic sperm injection with cryopreserved testicular spermatozoa.

Objective To assess the possibility of cryopreserving testicular tissue extracted sperm for intracytoplasmic sperm injection (ICSI). Design A report of two cases. Our study was approved by the Ethical Committee at the Instituto Valenciano de Infertilidad. Setting In vitro fertilization program at the Instituto Valenciano de Infertilidad. Patients Two azoospermic patients with severe spermatogenic failure but with focal spermatogenesis on testicular biopsies. In both cases, a first ICSI attempt with fresh testicular biopsy extracted sperm was unsuccessful. Interventions Cryopreservation of testicular spermatozoa in 100-µL "pills." Intracytoplasmic sperm injection with thawed testicular sperm…

Age and Uterine Receptiveness: Predicting the Outcome of Oocyte Donation Cycles

The impact of advancing age on uterine receptiveness has always been a concern of the medical establishment. Oocyte donation (OD) is the perfect model for ascertaining the extent of this relationship, but the literature is somewhat unreliable, mainly due to the limited samples on which the studies are based and insufficient control of important variables such as embryo quality.The present work was developed in a private infertility clinic.We retrospectively evaluate the results of 3089 OD cycles that ended up in a d 3 embryo transfer. Severe male factor infertility was an exclusion criterion.The impact of patients' age on pregnancy, implantation, and miscarriage rates and obstetric outcome …

High incidence of chromosomal abnormalities in large-headed and multiple-tailed spermatozoa

Rodrigo Vivo, Lorena, lorovi@alumni.uv.es ; Prados Dodd, Nicolas, Nicolas.Prados@uv.es ; Gil Salom, Manuel Luis, Manuel.Gil-Salom@uv.es ; Remohi Gimenez, Jose Alejandro, J.Alejandro.Remohi@uv.es

Intracytoplasmic Testicular Sperm Injection: An Effective Treatment for Otherwise Intractable Obstructive Azoospermia

AbstractPurpose: We evaluated the efficacy of intracytoplasmic sperm injection with testicular spermatozoa.Materials and Methods: Intracytoplasmic sperm injection was performed with spermatozoa obtained from testicular biopsy specimens in 15 patients with obstructive azoospermia, in whom standard microsurgical procedures were not feasible or had previously failed.Results: Fertilization was achieved in 14 to 15 cycles. Mean fertilization rate per cycle was 63.6 percent. Four clinical pregnancies occurred, for a pregnancy rate of 26.7 percent per started cycle and 28.6 percent per transfer.Conclusions: Intracytoplasmic testicular sperm injection is followed by high fertilization rates, and of…

GnRH agonist administration at the time of implantation does not improve pregnancy outcome in intrauterine insemination cycles: a randomized controlled trial.

Objective To assess whether GnRH agonist administration in the luteal phase improves pregnancy outcome in intrauterine insemination (IUI) cycles. Design Single-center, randomized, single-blind, placebo-controlled trial. Setting University-affiliated infertility clinic, between February 2005 and December 2007. Patient(s) Three hundred forty-four women undergoing IUI owing to mild to moderate male factor or donor sperm indication. Intervention(s) Random administration to either a single subcutaneous injection of 0.1 mg triptorelin (group A; n = 172) 8 days after hCG administration, or solvent only (group B; n=172) at the same time. Main Outcome Measure(s) Pregnancy rate was the primary outcom…

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…

Endometrial gene expression in the window of implantation is altered in obese women especially in association with polycystic ovary syndrome

Objective To determine whether luteal phase endometrial transcriptome is altered in obese women during the window of implantation (WOI), considering the presence of infertility, fat distribution and association with polycystic ovary syndrome (PCOS). Design Prospective study. Setting University-affiliated infertility clinic, between May 2007 and March 2009. Patient(s) One control group of women with normal weight (n = 4), and four study groups of obese women (n = 6 each one) according to the association with infertility, PCOS, and ovarian stimulation. Intervention(s) The endometrium was biopsied 7 days after LH surge or hCG administration in 28 women. Main Outcome Measure(s) Endometrial gene…

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…

P04.29: Is the finding of a central gall bladder an anatomic variant?

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…

Comparison between storage of vitrified oocytes by cryotop method in liquid nitrogen vs. vapour phase of liquid nitrogen tanks

F117Hystero-embryoscopic findings in early nonviable pregnancies

Background A high proportion of early pregnancy losses are associated to abnormal embryo development. However, chromosomal analysis of routine curettage samples are of limited value; and histopathological examinations of the embryos are rarely performed in clinical practice. Method A transcervical hystero-embryoscopy was performed prior to the curettage in 31 nonviable first-trimester pregnancies and a control group of 5 early terminations of pregnancy. In the study group, the estimated gestational age according to the ultrasound findings was 6.7 (4–9) menstrual weeks. Direct biopsies of different gestational structures were taken during the endoscopic procedure. Results In nonviable pregna…

Potential pitfalls in fetal neurosonography

Objective To present anatomic variants of the fetal brain and artifacts related to scanning techniques that could be misinterpreted as abnormalities on prenatal neurosonographic studies. Methods The findings were derived from fetal neurosonographic studies performed routinely from 16 to 36 weeks' gestation during the last 3 years, supervised by a sonologist specialized in neonatal cranial sonography. Results The pitfalls were divided into three groups: brain parenchyma, ventricular system and choroid plexus. We provide images of these pseudolesions and clues to their differentiation from true brain pathology. Conclusions Knowledge of misleading images seen on fetal neurosonographic studies …

The influence of oxygen concentration during embryo culture on obstetric and neonatal outcomes: a secondary analysis of a randomized controlled trial.

Abstract STUDY QUESTION Does oxygen concentration during 3-day embryo culture affect obstetric and neonatal outcomes? SUMMARY ANSWER Oxygen concentration during 3-day embryo culture does not seem to affect the obstetric and neonatal outcomes measured. WHAT IS KNOWN ALREADY Atmospheric oxygen appears to be harmful during extended embryo culture. Embryo culture conditions might therefore be a potential risk factor for subsequent fetal development and the health of future children. No data are available concerning the obstetrics and neonatal outcomes after Day 3 transfer of embryos cultured under reduced and atmospheric oxygen tensions. STUDY DESIGN, SIZE, DURATION A secondary analysis of a pr…

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…

An anatomical fetal brain structure and a normal variant mimicking anomalies on routine neurosonographic imaging: report of two cases

We present two cases in which an anatomical structure, the calcar avis, and a normal variant, a bifid choroid plexus, mimicked abnormalities on routine prenatal ultrasound examination. To the best of our knowledge these pitfalls have only been described in neonates. A familiarity with these false images is important to avoid erroneous diagnoses.

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…

Impact of luteinizing hormone administration on gonadotropin-releasing hormone antagonist cycles: an age-adjusted analysis

Objective: To analyze the impact of LH administration on cycle outcome in ovarian stimulation with GnRH antagonists. Design: Randomized, open-label, controlled trial performed in two age subgroups. Recombinant (r) FSH versus rFSH + rLH administration was compared. Setting: University-affiliated private infertility clinic. Patient(s): Up to 35 years old (n = 380) and aged 36 to 39 years (n = 340), undergoing their first or second IVF cycle. Intervention(s): Recombinant LH administration since stimulation day 1. Main Outcome Measure(s): Implantation rate, ongoing pregnancy rate. Result(s): In the young population, implantation rates were similar: 27.8% versus 28.6%, odds ratio (OR) 1.03 (95% …

Successful pregnancy and childbirth after intracytoplasmic sperm injection with calcium ionophore oocyte activation in a globozoospermic patient

Objective To check the effectiveness of intracytoplasmic sperm injection (ICSI) combined with assisted oocyte activation (AOA) in a globozoospermic patient. Design Case report. Setting Instituto Valenciano de Infertilidad, Valencia, Spain. Patient(s) A patient with globozoospermia. Intervention(s) ICSI was administered in 14 oocytes. ICSI combined with AOA, in which a small amount of calcium was injected followed by calcium ionophore exposure, was done in 9 oocytes. Main Outcome Measure(s) Fertilization rate and embryo quality was assessed in both groups. Result(s) Chemical activation increased fertilization rate (55.6% vs. 35.7%) and the number of embryos with less multinucleation on day 2…

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 …

Cervical pregnancy in assisted reproduction: an analysis of risk factors in 91,067 ongoing pregnancies

Abstract Research question What is the frequency of cervical pregnancy in women undergoing assisted reproductive technologies (ART) and what are the risk factors? Design Case-control study of women undergoing assisted reproductive technology (ART) at 25 private assisted reproduction clinics run by the same group in Spain. Two control groups (tubal ectopic pregnancies and intrauterine pregnancies) were established. The main outcome measure was frequency of cervical pregnancy. Demographic, clinical factors and IVF parameters were assessed for their influence on cervical pregnancy risk. Results Thirty-two clinical pregnancies were achieved out of 91,067 ongoing pregnancies, yielding a rate of …

Obesity and poor reproductive outcome: the potential role of the endometrium

Objective To analyze the potential role of extraovarian factors such as endometrium in the reproductive outcome of obese patients. Design Retrospective study. Setting University-affiliated infertility clinic, between January 2001 and July 2005. Patient(s) Women undergoing a total of 2656 first ovum donation (OD) cycles with good quality embryos. Intervention(s) The oocyte donors underwent controlled ovarian hyperstimulation, and recipients received a well-established hormonal replacement therapy for endometrial preparation. In vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) was performed according to semen characteristics. All first cycles (n = 2656) of ovum donation us…

Clinical experience and perinatal outcome of blastocyst transfer after coculture of human embryos with human endometrial epithelial cells: a 5-year follow-up study.

Abstract Objective To evaluate the reproductive and neonatal outcome of blastocyst transfer after coculture with human endometrial epithelial cells in IVF and oocyte donation. Design Retrospective study. Setting Private assisted reproductive center. Patient(s) Two hundred sixty women undergoing IVF and 469 oocyte recipients. Intervention(s) IVF or intracytoplasmic sperm injection (ICSI) and transfer of at least one blastocyst after coculture with human endometrial epithelial cells. Main outcome measure(s) Blastocyst formation rate, implantation and pregnancy rates, neonatal outcome, and congenital birth defects. Results Among patients who had transfer with their own oocytes, 1,193 of 2,349 …

F33Application of early sonographic markers of Down syndrome to pregnancies achieved by assisted reproduction techniques

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…

Have Day 3 Embryo Morphology a Predictive Value in Blastocyst Formation?

Effect of different cryopreservation protocols on the metaphase II spindle in human oocytes.

The aim of this study was to evaluate the impact of different cryopreservation protocols on the repolymerization of metaphase (M)II spindles in human oocytes. Fresh aspirated donor oocytes were cryopreserved 3–4 h after retrieval using four different protocols: slow freezing using 1.5 mol/l 1,2-propanediol (PROH) + 0.2 mol/l sucrose (n = 36); 1.5 mol/l PROH + 0.3 mol/l sucrose (n = 34); 1.5 mol/l PROH + 0.3 mol/l sucrose with Na + depleted–choline replaced media (n = 27), and vitrification by the Cryotip method (n = 23). The control group comprised 34 fresh oocytes. Three hours after thawing, surviving and control oocytes were fixed for meiotic spindle/chromatin assessment. Survival rates w…

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.

Evidence-based medicine is gaining momentum

Vitrification of preimplantation genetically diagnosed human blastocysts and its contribution to the cumulative ongoing pregnancy rate per cycle by using a closed device.

Objective To evaluate the survival rate and clinical results of our vitrification procedure on preimplantation genetic diagnosis (PGD) blastocysts and to calculate its actual contribution to the reproductive outcome per cycle. Design Retrospective clinical study. Setting University Institute IVI, Valencia, Spain. Patient(s) Patients who requested cryotransfer of surplus PGD blastocysts after failed fresh elective transfer. Intervention(s) Retrospectively collected data during 2 years of experience with blastocyst vitrification. Main Outcome Measure(s) Primary outcome measures were the following: blastocyst recovery and survival; cryotransfer cancellation; and the implantation, pregnancy (PR…

The Human Blastocyst Regulates Endometrial Epithelial Apoptosis in Embryonic Adhesion1

The implanting blastocyst must appose and adhere to the endometrial epithelium and, subsequently, invade it. Locally regulated uterine epithelial apoptosis induced by the embryo is a crucial step of the epithelial invasion in rodents. To address the physiological relevance of this process in humans, we investigated the effect of single human blastocysts on the regulation of apoptosis in cultured human endometrial epithelial cells (hEEC) in both apposition and adhesion phases of implantation. Here, we report a co-ordinated embryonic regulation of hEEC apoptosis. In the apposition phase, the presence of a blastocyst rescues hEEC from the apoptotic pathway. However, when the human blastocyst a…

Comparison of concomitant outcome achieved with fresh and cryopreserved donor oocytes vitrified by the Cryotop method

Objective To evaluate the outcome of oocyte vitrification using the Cryotop method, observed in an egg donation program by simultaneously evaluating embryos derived from vitrified and fresh oocytes coming from the same stimulated cycle. Design Cohort prospective randomized study. Setting Instituto Valenciano de Infertilidad (IVI) Valencia, Spain. Patient(s) Thirty oocyte donors and 30 recipients with informed consents. Intervention(s) Vitrification by the Cryotop method. Warming 1 hour after vitrification. Microinjection of surviving MII and fresh oocytes, evaluation of fertilization, embryo development, and clinical results. Main Outcome Measure(s) Survival, fertilization, and cleavage rat…

Intracytoplasmic sperm injection with cryopreserved testicular spermatozoa

To assess if testicular sperm cryopreservation is a valid alternative to repetition of testicular sperm retrieval techniques, results of a cryopreservation technique in pills have been retrospectively analyzed. Enough motile spermatozoa for ICSI were obtained in 172 from 190 (90.5%) frozen-thawed testicular sperm samples. Overall, 249 couples underwent 390 ICSI cycles, 156 using fresh and 234 using cryopreserved testicular sperm. Mean two-pronuclear fertilization rates per cycle were not significantly different after ICSI with fresh (62.0%) or with cryopreserved (63.2%) spermatozoa. Mean embryo cleavage rate per cycle was higher in the fresh (90.6%) than in the cryopreserved (84.6%) group (…

Radicales libres de oxígeno y su relación con enfermedades específicas del embarazo

Resumen De forma reciente se han publicado estudios que relacionan los radicales libres de oxigeno con enfermedades especificas del embarazo. En el parto pretermino, el oxido nitrico puede estar involucrado en la quiescencia fisiologica del utero y la colagenolisis asociada con el reblandecimiento tisular del cervix. Respecto a la rotura prematura de membranas, se conoce que la fuerza del amnios deriva del colageno; que su degradacion es controlada por las metaloproteinasas de la matriz, y que una alteracion del balance entre los pro y los antioxidantes aumenta la actividad de estas ultimas. En la preeclampsia, la placentacion defectuosa produce vasoconstriccion, con baja perfusion placenta…

Effect of vitrification on human oocytes: a metabolic profiling study.

Objective To evaluate the effect of oocyte vitrification in the metabolomic profile of embryos developed from vitrified and fresh oocytes in our ovum donation program. Design Analysis of the metabolic profiles of spent culture medium samples corresponding to embryos developed from vitrified and fresh oocytes. Setting In vitro fertilization (IVF) unit/metabolomic facility. Patient(s) Oocyte donors between the ages of 18 and 35 years. Intervention(s) Metabolomic profile liquid chromatography coupled with mass spectrometry (LC-MS) of spent media samples. Main Outcome Measure(s) Identification of spent media components and metabolites present and absent in vitrified and fresh day-3 embryos. Res…

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…

First-trimester reversed end-diastolic flow in the umbilical artery is not always an ominous sign

We report five cases of first-trimester reversed end-diastolic flow in the umbilical artery. Diagnoses were performed between 8 and 12 gestational weeks. All but one case appeared as a transient early finding. Second-trimester fetal demise occurred in two cases. One case delivered at 32 weeks with severe growth restriction but recovered well. The other two cases had a good pregnancy outcome. Our experience suggests that this early Doppler finding is not always an ominous sign.

Testicular sperm from patients with obstructive and nonobstructive azoospermia: aneuploidy risk and reproductive prognosis using testicular sperm from fertile donors as control samples.

Objective To establish a baseline incidence of chromosomal abnormalities in testicular sperm of fertile men and to determine the best control sample for comparisons with azoospermic males to estimate their reproductive prognosis. Design Prospective study. Setting Infertility clinic. Patient(s) Sixteen obstructive azoospermic (OA) and 19 nonobstructive azoospermic patients (NOA). Control samples were ejaculated sperm from ten fertile donors and testicular sperm from ten other fertile donors. Intervention(s) Fluorescence in situ hybridization (FISH) in sperm. Main Outcome Measure(s) Sperm numerical abnormalities for chromosomes 13, 18, 21, X, and Y; ongoing implantation and pregnancy rates in…

Evidence that the endometrial microbiota has an effect on implantation success or failure

Background Bacterial cells in the human body account for 1–3% of total body weight and are at least equal in number to human cells. Recent research has focused on understanding how the different bacterial communities in the body (eg, gut, respiratory, skin, and vaginal microbiomes) predispose to health and disease. The microbiota of the reproductive tract has been inferred from the vaginal bacterial communities, and the uterus has been classically considered a sterile cavity. However, while the vaginal microbiota has been investigated in depth, there is a paucity of consistent data regarding the existence of an endometrial microbiota and its possible impact in reproductive function. Objecti…

Embryo effects in human implantation: embryonic regulation of endometrial molecules in human implantation.

: Embryonic implantation requires coordinated development of the blastocyst and the maternal endometrium. Considerable advances have been made in the understanding of the cell biology of human embryo and maternal endometrium as separate entities. Nevertheless, communication between them and their reciprocal effects on each other constitute an exciting and as-yet unsolved problem in reproductive medicine. Cross-talk among the embryo, endometrium, and the corpus luteum are known to occur in ruminants and primates; more specifically, endometrial-embryonic interactions have been reported in rodents and primates. Here, we present updated information in humans on the embryonic regulation of endom…

El coasting es eficaz en la prevención del síndrome de hiperestimulación ovárica y no afecta a los resultados de la fecundación in vitro

Resumen Objetivo Describir los resultados de los ciclos de FIV/ICSI en pacientes sometidas a coasting por hiperrespuesta a la estimulacion ovarica controlada (EOC), asi como la frecuencia de presentacion y severidad del sindrome de hiperestimulacion ovarica (SHO). Ademas, evaluar si la duracion del coasting compromete los resultados del ciclo Pacientes y metodos Estudio retrospectivo de 42 ciclos de fecundacion in vitro de pacientes con hiperrespuesta a la EOC sometidas a coasting (mantener la administracion del analogo de la GnRH mientras se suprime la administracion de gonadotropinas) hasta que los valores sericos de estradiol (E2) disminuyan a un valor “seguro” para administrar la hCG y …

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 …

Asynchronous and pathological windows of implantation: two causes of recurrent implantation failure

STUDY QUESTION: Is endometrial recurrent implantation failure (RIF) only a matter of an asynchronous (displaced) window of implantation (WOI), or could it also be a pathological (disrupted) WOI? SUMMARY ANSWER: Our predictive results demonstrate that both displaced and disrupted WOIs exist and can present independently or together in the same RIF patient. WHAT IS KNOWN ALREADY: Since 2002, many gene expression signatures associated with endometrial receptivity and RIF have been described. Endometrial transcriptomics prediction has been applied to the human WOI in two previous studies. One study describes endometrial RIF to be the result of a temporal displacement of the WOI. The other indic…

New options in assisted reproduction technology: the Cryotop method of oocyte vitrification

The Cryotop vitrification method has been shown to be a very useful tool for oocyte cryopreservation, giving excellent results regarding survival and clinical outcome. There are several clinical situations in which oocyte cryopreservation provides solutions that have not been available to date. This report describes three of these situations: (i) a low-responder patient who needed a single gene diagnosis due to the presence of a genetic disease; (ii) a patient undergoing endometrial bleeding on the day of oocyte retrieval who was also affected by a genetic disorder; and (iii) a patient who failed to become pregnant after the donation of vitrified oocytes and subsequently had the re-vitrifie…

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…

P03.04: The influence of mode of conception, fetal gender and twin pregnancy in the development of cerebral structures: a fetal brain 3D ultrasound study

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…

TESTICULAR SPERM EXTRACTION AND INTRACYTOPLASMIC SPERM INJECTION

We evaluate the efficacy of testicular sperm extraction and results of intracytoplasmic sperm injection in cases of nonobstructive azoospermia. In addition, we define predictive parameters for successful testicular sperm extraction in these patients.A total of 154 patients with nonobstructive azoospermia underwent multiple testicular biopsies to obtain testicular spermatozoa and for histopathological diagnosis. Results of testicular sperm extraction were related to suspected etiology of azoospermia, patient age, maximal testicular volume, serum follicle-stimulating hormone and histopathology. When testicular sperm extraction was successful, intracytoplasmic sperm injection was performed.Spe…

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 …

Obstetric and perinatal outcome of babies born from vitrified oocytes.

Objective To assess outcomes after oocyte vitrification on obstetric and perinatal outcomes compared with those achieved with fresh oocytes. Design Retrospective cohort study. Setting Private university-affiliated IVF center. Patient(s) Children born after use of vitrified oocytes (1,027 from 804 pregnancies) and fresh oocytes (1,224 from 996 pregnancies). Singleton and multiples pregnancies from own and donated ova were included. Intervention(s) Oocyte vitrification by the Cryotop method. Main Outcome Measure(s) Pregnancy, delivery, and neonatal outcomes. Result(s) Vitrification had no clinically relevant adverse effects on obstetric and perinatal outcomes after adjusting for potential con…

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…

Pregnancy in an azoospermic patient with markedly elevated serum follicle-stimulating hormone levels

Objective To assess the possibility of achieving a pregnancy in an azoospermic patient with markedly elevated serum FSH level. Design A case report. Setting In vitro fertilization program at the Instituto Valenciano de Infertilidad. Patient An azoospermic patient with small testes and serum FSH level (38.7 mlU/mL) higher than three times normal. Testicular biopsy revealed Sertoli cell-only syndrome with focal spermatogenesis. Interventions Intracytoplasmic microinjection of testicular tissue-extracted spermatozoa. Main Outcome Measurements: Fertilization rate, cleavage rate, clinical pregnancy. Results Eight of 11 (73%) intact oocytes showed two pronuclei. All of them cleaved normally. Four…

Impact of preimplantation genetic diagnosis on IVF outcome in implantation failure patients

Implantation failure (IF) is defined as three or more failed IVF attempts, and preimplantation genetic diagnosis (PGD) is being used in these patients to improve IVF outcome. PGD was performed in 49 implantation failure patients with a mean number of 4.2 +/- 1.6 previous IVF failures, and in nine fertile controls. Fluorescence in-situ hybridization (FISH) on blastomeres from biopsied day 3 embryos was performed for chromosomes 13, 16, 18, 21, 22, X and Y. There was a significantly higher rate of chromosomal abnormalities (67.4%) compared with controls (36.3%). In 57 cycles, a pregnancy rate of 34.0% and an implantation rate of 19.8% was observed in implantation failure patients compared wit…

Ultrastructure of preimplantation genetic diagnosis-derived human blastocysts grown in a coculture system after vitrification

Objective To evaluate ultrastructural features of preimplantation genetic diagnosis (PGD) blastocysts before and after vitrification. Design Descriptive study of both vitrified and fresh hatching blastocysts. Setting PGD program at the Instituto Universitario, Instituto Valenciano de Infertilidad. Patient(s) Patients undergoing PGD donated their abnormal embryos for research (n = 26). Intervention(s) Biopsied embryos were cultured in the presence of human endometrial cells until day 6. Sixteen blastocysts were vitrified. A total of 11 high-scored hatching blastocysts, 6 warmed and 5 fresh, were fixed for ultrastructure. Main Outcome Measure(s) The cytoskeleton structure, type of intercellul…

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…

Intracytoplasmic sperm injection: a treatment for extreme oligospermia.

AbstractPurpose: We evaluated the efficacy of intracytoplasmic sperm injection in patients with extreme oligospermia.Materials and Methods: A total of 67 intracytoplasmic sperm injection cycles was attempted in 58 infertile couples in which the husbands had extreme oligospermia (less than 100,000 spermatozoa per ml. ejaculate).Results: Fertilization was achieved in 65 of 67 cycles. Mean fertilization rate per cycle was 66.4 percent. A total of 18 clinical pregnancies was obtained, for a pregnancy rate of 26.8 percent per started cycle. There were 4 miscarriages and 8 live births from 5 deliveries. Nine pregnancies are ongoing.Conclusions: Intracytoplasmic sperm injection in patients with ex…

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,…

Number needed to freeze: cumulative live birth rate after fertility preservation in women with endometriosis

Research question: How does the number of oocytes used affect the cumulative live birth rate in endometriosis patients who had their oocytes vitrified for fertility preservation (FP)? Design: Retrospective observational study including data from 485 women with endometriosis who underwent FP from January 2007 to July 2018. Survival curves and Kaplan-Meier plots were used to analyse the cumulative live birth rate (CLBR) according to the number of vitrified oocytes used. Data were stratified according to age, stage of the disease and ovarian surgery prior to FP (operated vs. non-operated). Endometriosis curves were compared to plots developed using elective fertility preservation (EFP) patient…