P–435 LH preserves oocyte-granulosa cell communication in mouse ovaries exposed to chemotherapy with alkylating agents

Abstract Study question Does Luteinizing Hormone (LH) protect the follicular endowment and growth by improving oocyte-granulosa cell (GC) communication of follicles exposed to chemotherapy at the primordial stage? Summary answer LH treatment protects mouse primordial follicles against alkylating agents by preventing the chemotherapy-induced follicular depletion and the impairment of oocyte-GC communication during follicular growth. What is known already Impaired folliculogenesis is one of the most common deleterious side effects of alkylating agents in ovaries. Bidirectional communication between the oocyte and surrounding GCs is crucial for oocyte development. Therefore, defective gap junc…

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…

Elective single versus double embryo transfer: live birth outcome and patient acceptance in a prospective randomised trial

The purpose of this study was to determine which strategy of embryo transfer has a better trade-off in live birth delivery rate versus multiple pregnancy considering patient acceptance: elective single embryo transfer (eSET) or elective double embryo transfer (eDET). In all, 199 women <38 years of age undergoing their first IVF treatment in a private centre were included in a prospective open-label randomised controlled trial. Patients were randomised into four groups: (1) eSET on Day 3; (2) eSET on Day 5; (3) eDET on Day 3; and (4) eDET on Day 5. Per patient, main analysis included acceptance of assigned group, as well as multiple and live birth delivery rates of the fresh cycle. Second…

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…

OP09.10: Hemodynamic effects of sildenafil administration in an animal model of preeclampsia

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…

Increased doses of vaginal progesterone for the prevention of preterm birth in twin pregnancies: a randomised controlled double-blind multicentre trial

Objective  Previous trials have shown little benefit for preventing preterm birth in twin pregnancies using 90–200 mg of daily vaginal natural progesterone. Higher doses have not been tested. Our aim was to determine the efficacy and safety of two different daily doses of vaginal natural progesterone (200 and 400 mg), compared with placebo, for preventing preterm birth in unselected twin pregnancies. Design  Randomised controlled double-blind multicentre trial (1:1:1). Setting  The study was carried out in five university centres from Valencia, Murcia and Alicante (Spain). Population  Women with dichorionic diamniotic twin pregnancies. Methods  The women self-inserted two vaginal pessaries …

Autologous stem cell ovarian transplantation to increase reproductive potential in patients who are poor responders.

Objective: To evaluate effects of autologous stem cell ovarian transplant (ASCOT) on ovarian reserve and IVF outcomes of women who arc poor responders with very poor prognosis. Design: Prospective observational pilot study. Setting: University hospital. Patient(s): Seventeen women who are poor responders. Intervention(s): Ovarian infusion of bone marrow-derived stem cells. Main Outcome Measure(s): Serum antimullerian hormone levels and antral follicular count (AFC), punctured follicles, and oocytes retrieved after stimulation (controlled ovarian stimulation) were measred. Apheresis was analyzed for growth factor concentrations. Result(s): The ASCOT resulted in a significant improvement in A…

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…

Dopamine receptor 2 activation inhibits ovarian vascular endothelial growth factor secretion in vitro: implications for treatment of ovarian hyperstimulation syndrome with dopamine receptor 2 agonists

Objective To ascertain whether vascular endothelial growth factor (VEGF) secretion by luteinized granulosa cells (GCs) is modulated by the dopaminergic system in a dose-dependent fashion and how this is related to the differential efficacy of dopamine receptor 2 (D2)-agonists (D2-ag) in preventing ovarian hyperstimulation syndrome (OHSS). Design The relationship between the dopaminergic system and VEGF secretion in luteinized GCs was evaluated. Archived human ovaries were immunostained to characterize D2 expression. Setting University affiliated infertility center. Patient(s) Premenopausal women and egg donors. Intervention(s) Luteinized GCs were cultured with the D2-ag cabergoline. Human o…

Kinetics of the early development of uniparental human haploid embryos

Objective: To describe morphokinetically the early development of human haploid parthenotes and androgenotes and to compare them with euploid embryos. Design: Experimental study of kinetics. Setting: University-affiliated private fertility center. Patient(s): Experimental haploid parthenotes and androgenotes. Intervention(s): Kinetic study of early development (up to eight cells) of 8 parthenotes, 10 androgenotes, and 20 euploid embryos. Main Outcome Measure(s): Timing of the first seven cleavages determined according to embryo origin, then calculation of the duration of the second and third cell cycles (cc2 and cc3) of whole embryos and individual cells. Result(s): Parthenotes and androgen…

Inhibition of tumor cell proliferation in human uterine leiomyomas by vitamin D via Wnt/β-catenin pathway.

To assess the effect of vitamin D (VitD) on human uterine leiomyomas through Wnt/β-catenin pathway inhibition, apoptosis induction, and cell growth arrest.A prospective study comparing leiomyoma vs. myometrium tissues. Paired design study comparing human uterine leiomyoma primary (HULP) cells treated with or without VitD.University hospital.Human uterine leiomyoma and myometrium were collected from women (aged 35-52 years) without hormonal treatment.Samples were collected from women undergoing surgery due to symptomatic uterine leiomyoma pathology.Uterine leiomyoma and myometrium tissues were analyzed by western blot (WB) to determine proliferation, Wnt/β-catenin, and apoptosis pathways. HU…

Bioengineered endometrial hydrogels with growth factors promote tissue regeneration and restore fertility in murine models

Extracellular matrix (ECM) hydrogels obtained from decellularized tissues are promising biocompatible materials for tissue regeneration. These biomaterials may provide important options for endometrial pathologies such as Asherman's syndrome and endometrial atrophy, which lack effective therapies thus far. First, we performed a proteomic analysis of a decellularized endometrial porcine hydrogel (EndoECM) to describe the specific role of ECM proteins related to regenerative processes. Furthermore, we investigated the ability of a bioengineered system-EndoECM alone or supplemented with growth factors (GFs)-to repair the endometrium in a murine model of endometrial damage. For this model, the …

Assessment of the implantation of day-2 human embryos by morphometric nonsubjective parameters

Objective: To demonstrate the usefulness of image analysis in designing objective embryonic morphometric variables. Design: Retrospective study of 214 top-quality day-2 embryo photographs from 50 double-embryo transfers resulting in no pregnancy (group 0) and 57 resulting in twin pregnancy (group 1). Setting: Human reproduction unit. Patient(s): Study of 107 in vitro fertilization intracytoplasmic sperm injection (IVF ICSI) cycles in women age<36 years with doubleembryo transfer of top-quality embryos. Only the first cycle of IVF ICSI was included. Intervention(s): Standard IVF ICSI protocols. Main Outcome Measure(s): The embryo photographs were analyzed using the ImageJ program. The effect…

Is ovarian stimulation detrimental to the endometrium?

Ovarian stimulation in assisted reproduction technology produces lower implantation rates per embryo transferred than natural and ovum donation cycles, suggesting suboptimal endometrial development due to the abnormal concentrations of hormones used to recruit more oocytes. After the publication of several studies on the gene expression profile of endometrial receptivity in the natural cycle using microarray technology, researchers have investigated the impact of ovarian stimulation on the gene expression pattern of the endometrium. Ovarian stimulation cycles that use gonadotrophin-releasing hormone (GnRH) agonists and antagonists have been analysed in detail during the window of implantati…

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…

Stem Cells and the Endometrium: From the Discovery of Adult Stem Cells to Pre-Clinical Models.

Adult stem cells (ASCs) were long suspected to exist in the endometrium. Indeed, several types of endometrial ASCs were identified in rodents and humans through diverse isolation and characterization techniques. Putative stromal and epithelial stem cell niches were identified in murine models using label-retention techniques. In humans, functional methods (clonogenicity, long-term culture, and multi-lineage differentiation assays) and stem cell markers (CD146, SUSD2/W5C5, LGR5, NTPDase2, SSEA-1, or N-cadherin) facilitated the identification of three main types of endogenous endometrial ASCs: stromal, epithelial progenitor, and endothelial stem cells. Further, exogenous populations of stem c…

The role of the leptin in reproduction.

Since its discovery in 1994, leptin has appeared to be a pleiotrophic hormone, governing energy homeostasis and affecting many tissues in the body. Numerous pieces of evidence have accumulated showing that leptin potentially plays an important role in the control of the reproductive function.This review presents the major concepts for the role of leptin in the modulation of reproductive function. As a marker of the nutritional status, leptin affects the hypothalamo-pituitary-gonadal axis, regulating gonadotrophin-releasing hormone and luteinising hormone secretion, and appears to be a permissive factor in the onset of the puberty. This protein and its receptor have been found in the reprodu…

Plasma levels of soluble vascular endothelial growth factor receptor-1 may determine the onset of early and late ovarian hyperstimulation syndrome

BACKGROUND Ovarian hyperstimulation syndrome (OHSS) is a life-threatening condition associated with ovarian stimulation. Its pathophysiology is unknown and its treatment continues to be empirical. Early (E)- and late (L)-OHSS occur in women at risk, though not in all cases. Vascular endothelial growth factor (VEGF) is related to increased vascular permeability in OHSS. We analysed the dynamics of the VEGF system in E- and L-OHSS. METHODS A prospective cohort of women undergoing IVF-ICSI treatment were divided into groups. E-OHSS: Nonpregnant patients classified as women not at risk (group 1) (n = 11) and patients at risk who did not (group 2) (n = 18) and did (group 3) (n = 8) develop sever…

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.…

cGMP modulates stem cells differentiation to neurons in brain in vivo pathological implications

During brain development there is a strict control of the proliferation, migration and differentiation of neural stem cells to different cell types. Alterations in the control of these processes may result in altered balance in the formation of different cell types resulting in a long-lasting impairment of cerebral processes. This occurs for example if brain is exposed to alcohol during key stages of development which results in accelerated glial cells formation, impaired neuron formation and impaired cognitive function. The molecular mechanisms modulating differentiation of neural stem cells to neurons or non neuronal cells are not well known. Nitric oxide (NO) plays a relevant role in thi…

Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) typically occurs when ovaries are primed with FSH/ LH and subsequently exposed to hCG. The ultimate pathophysiological step underlying this clinical picture is increased vascular permeability (VP). METHODS: A search of the literature was carried out using PubMed and the authors’ files. RESULTS: In rodents and humans, the expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) mRNA increases during ovarian stimulation. With the administration of hCG, the expression of each rises to a maximum. Expression of VEGF/VEGFR-2 mRNAs correlates with enhanced VP, with both peaking 48 h following an injection of hCG. Imm…

IMPACT OF ULTRASOUND DIAGNOSIS OF ADENOMYOSIS ON PREGNANCY RATE AND OUTCOME IN IVF CYCLES WITH DONATED OOCYTES: A PROSPECTIVE STUDY

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…

Identification and characterization of the human leiomyoma side population as putative tumor-initiating cells.

Objective To isolate and characterize human leiomyoma stem cells by the side population (SP) method. Design Prospective experimental human and animal study. Setting University research laboratory-affiliated infertility clinic. Patient(s) Women undergoing laparoscopic myomectomy. Animal(s) Female non-obese diabetic severe combined immune deficiency (NOD-SCID) mutation mice. Intervention(s) Obtainment of human leiomyoma SP cells as candidate tumor-initiating cells and establishment of two leiomyoma SP lines. Main Outcome Measure(s) Flow cytometry, semiquantitative polymerase chain reaction, clonogenicity assays, cDNA microarrays hybridization, cell culture, karyotype, molecular analysis, immu…

First report on fertility after allogeneic uterus transplantation

Uterus transplantation may become the first available treatment for uterine factor infertility, which is due to the absence or malfunction of the uterus. Here we describe for the first time pregnancy after allogeneic uterus transplantation, as a proof of concept of uterine function in a transplanted uterus in a standardized animal model (rat) under immunosuppression.

The cyto-protective effects of LH on ovarian reserve and female fertility during exposure to gonadotoxic alkylating agents in an adult mouse model.

Abstract STUDY QUESTION Does LH protect mouse oocytes and female fertility from alkylating chemotherapy? SUMMARY ANSWER LH treatment before and during chemotherapy prevents detrimental effects on follicles and reproductive lifespan. WHAT IS KNOWN ALREADY Chemotherapies can damage the ovary, resulting in premature ovarian failure and reduced fertility in cancer survivors. LH was recently suggested to protect prepubertal mouse follicles from chemotoxic effects of cisplatin treatment. STUDY DESIGN, SIZE, DURATION This experimental study investigated LH effects on primordial follicles exposed to chemotherapy. Seven-week-old CD-1 female mice were randomly allocated to four experimental groups: C…

A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature

Objective: To create a genomic tool composed of a customized microarray and a bioinformatic predictor for endometrial dating and to detect pathologies of endometrial origin. To define the transcriptomic signature of human endometrial receptivity. Design: Two cohorts of endometrial samples along the menstrual cycle were used: one to select the genes to be included in the customized microarray (endometrial receptivity array [ERA]), and the other to be analyzed by ERA to train the predictor for endometrial dating and to define the transcriptomic signature. A third cohort including pathological endometrial samples was used to train the predictor for pathological classification. Setting: Healthy…

Human endometrial CD98 is essential for blastocyst adhesion.

Background Understanding the molecular basis of embryonic implantation is of great clinical and biological relevance. Little is currently known about the adhesion receptors that determine endometrial receptivity for embryonic implantation in humans. Methods and Principal Findings Using two human endometrial cell lines characterized by low and high receptivity, we identified the membrane receptor CD98 as a novel molecule selectively and significantly associated with the receptive phenotype. In human endometrial samples, CD98 was the only molecule studied whose expression was restricted to the implantation window in human endometrial tissue. CD98 expression was restricted to the apical surfac…

miRNA Signature and Dicer Requirement during Human Endometrial Stromal Decidualization In Vitro

Decidualization is a morphological and biochemical transformation of endometrial stromal fibroblast into differentiated decidual cells, which is critical for embryo implantation and pregnancy establishment. The complex regulatory networks have been elucidated at both the transcriptome and the proteome levels, however very little is known about the post-transcriptional regulation of this process. miRNAs regulate multiple physiological pathways and their de-regulation is associated with human disorders including gynaecological conditions such as endometriosis and preeclampsia. In this study we profile the miRNAs expression throughout human endometrial stromal (hESCs) decidualization and analy…

The use of prediction models of spontaneous pregnancy in in vitro fertilization units reveals differences between the expected results of public and private clinics in Spain.

To evaluate the applicability of prediction models (PM) of spontaneous pregnancy (SP) in a population of infertile patients from a university-affiliated private assisted reproductive technology center (Instituto Valenciano de Infertilidad) and in the reproductive medicine section of a public university hospital (La Fe), both belonging to the same city (Valencia, Spain) between January and December 2008. We calculated the probability of SP using the PM developed by Hunault et al. in our two populations, and observed an estimated probability of SP40% or the PM applicable in approximately 97% of the studied couples, and statistical differences between pregnancy probabilities in the two setting…

Dopamine agonist cabergoline reduces hemoconcentration and ascites in hyperstimulated women undergoing assisted reproduction.

Abstract Context: Ovarian hyperstimulation syndrome (OHSS) results from increased vascular permeability (VP) caused by ovarian hypersecretion of vascular endothelial growth factor (VEGF), which activates its receptor-2. In animals, the dopamine receptor 2 agonist cabergoline (Cb2) inactivates VEGF receptor-2 and prevents increased VP. Objective: Our objective was to test whether Cb2 reduces VP and prevents OHSS in humans. Design: We conducted a prospective, randomized, double-blind study on oocyte donors at risk of developing OHSS (&amp;gt;20 follicles, &amp;gt;12 mm developed, and &amp;gt;20 oocytes retrieved). Interventions: Cb2 0.5 mg/d (n = 37) or a placebo (n = 32) was administered fro…

New methods to improve the safety assessment of cryopreserved ovarian tissue for fertility preservation in breast cancer patients

Objective To develop a novel molecular panel of markers to detect breast cancer (BC) disseminated malignant cells in ovarian tissue, and to improve the safety of ovarian tissue transplantation. Design Experimental study. Setting University hospital. Patient(s) Ten ovarian biopsies from healthy patients, 13 biopsies with diagnosed BC metastasis, and 4 biopsies from primary BC tumor for designing a diagnostic panel of BC cell contamination; 60 ovarian biopsies from BC patients undergoing fertility preservation for validating the panel. Animal(s) Female nude mice. Intervention(s) A novel panel for BC malignant cell detection by reverse-transcription polymerase chain reaction (RT-PCR), inmmunoh…

Long-term vitamin D treatment decreases human uterine leiomyoma size in a xenograft animal model

Objective To study the effects of short- and long-term vitamin D treatment on uterine leiomyomas in vivo through cell proliferation, extracellular matrix (ECM) degradation, and apoptosis. Design Preclinical study of human leiomyoma treatment with vitamin D in an nonhuman animal model. Setting Hospital and university laboratories. Patient(s)/Animal(s) Human leiomyomas were collected from patients and implanted in ovariectomized NOD-SCID mice. Intervention(s) Mice were treated with vitamin D (0.5 μg/kg/d or 1 μg/kg/d) or vehicle for 21 or 60 days. Main Outcome Measure(s) Vitamin D effect in xenograft tissue was assessed by monitoring tumor size (18F-FDG positron-emission tomography/computeriz…

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…

Inhibition of KIF20A by BKS0349 reduces endometriotic lesions in a xenograft mouse model

AbstractSeveral studies have suggested a possible etiological association between ovarian endometriosis and ovarian cancer. Evidence has shown that KIF20A overexpression might confer a malignant phenotype to ovarian tumors by promoting proliferation and inhibiting apoptosis. However, no data about the role of KIF20A in endometriosis have been described. In this study, the human endometrium (n = 4) was transfected by mCherry adenovirus and intraperitoneally implanted in mice. Subsequently, mice were divided in three groups (n = 8/group) that were treated with Vehicle, BKS0349 (KIF20A-antagonist) or cabergoline (dopamine receptor agonist) for 21 days. mCherry-labeled endometriotic lesions wer…

Thirty-five years later, the first assisted reproductive technology program opens in Cambodia

Effect of Antiangeogenic Treatment on Peritoneal Endometriosis-Associated Nerve Fibers

Effect of an intrauterine device on the gene expression profile of the endometrium.

The human endometrium acquires the ability to allow embryo attachment just for a specific period of time during each menstrual cycle. Understanding of the opposite functional status, referred to as refractoriness, can potentially be used to improve receptivity in infertile patients or as an interceptive approach to prevent gestation.The objective of the study was to analyze the endometrial gene expression profile induced by an inert intrauterine device (IUD) at the time of implantation.We used a microarray containing more than 16,000 cDNAs to investigate the gene expression profile of receptive vs. refractory endometrium in the same women induced by the presence of an IUD. We compared the g…

Cigarette Consumption and X-Sperm Enrichment After Swim-Up

Vitamin d long-term treatment decreases human uterine leiomyoma size through specific molecular mechanisms in a xenograft animal model

Combined use of uterine artery embolization and local methotrexate injection in interstitial ectopic pregnancies with poor prognosis.

Objective To report three cases of interstitial pregnancies treated successfully by combining uterine artery embolization (UAE) and ultrasound-guided local administration of methotrexate (MTX); and to assess the effect of UAE on ovarian reserve by prospectively measuring serum antimullerian hormone (AMH) levels. Design Case report. Setting Departments of obstetrics and gynecology and radiology of a university hospital. Patient(s) Three patients with interstitial pregnancy. Treatment with multiple IM injections of MTX had failed in cases 1 and 3. Case 2 presented high initial serum β-hCG levels (93,563 mIU/mL), suggesting the presence of a substantial amount of trophoblastic tissue. Interven…

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…

Pharmacologic therapies in endometriosis: a systematic review

To assess the literature on preclinical and clinical efficacy and safety data of pharmacologic groups proposed in the treatment of endometriosis, we performed a systematic review of publications from March 2002 to January 2012 via PubMed search. Additional relevant articles were identified from citations within these publications. A high number of medications were tested in preclinical models of endometriosis due to their theoretic capacity of disrupting important pathophysiologic pathways of the disease, such as inflammatory response, angiogenesis and cell survival, proliferation, migration, adhesion, and invasion. Tumor necrosis factor α-blockers, nuclear factor κB inhibitors, antiangioge…

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

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 …

Prevention of OHSS: Current strategies and new insights

Abstract Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life threatening condition that affects young healthy patients. Many strategies have been proposed to prevent this syndrome. However, to avoid OHSS without compromising on IVF outcome is still a challenge. The most important action is to identify patients at risk even before ovarian stimulation is initiated and to give them special attention. Coasting is the most popular method to avoid/minimize OHSS. Cycle cancellation, cryopreservation, GnRH antagonists, GnRH agonists, i.v. albumin are other strategies that can provide some kind of benefit but do not completely avoid both early and late forms of OHSS and/or…

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…

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…

Does transvaginal color Doppler sonography differentiate between developing and involuting ectopic pregnancies?

The objective of this study was to assess the addition of transvaginal color Doppler imaging to transvaginal ultrasonography and beta-human chorionic gonadotropin values to differentiate between developin and involuting ectopic pregnancies. Forty surgically confirmed ectopic pregnancies were classified into developing or involuting according to histopathologic findings. Results were compared retrospectively with the plasma beta-human chorionic gonadotropin values as well as the resistive index and pulsatility index obtained in corpora lutea and peritrophoblastic flow in serial examinations. Student's t-test was used for comparison of means. Logistic regression analysis was applied to predic…

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) …

Evaluation of the potential therapeutic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of endometriosis.

Objective To assess the therapeutic potential of polyinosine-polycytidylic acid, a double-stranded RNA molecule with selective proapoptotic and antiangiogenic activity, complexed with polyethyleneimine (pIC PEI ) in treating endometriosis. Design A heterologous mouse model of endometriosis was created by injecting human endometrial fragments into the peritoneum. Endometrial fragments were engineered to express the fluorescent protein mCherry as a reporter to monitor status over the course of the 4-week study. Setting University-affiliated infertility center. Animal(s) Ovariectomized and hormone-replaced nude mice (n = 30) injected with fluorescent-labeled human endometrial fragments at 4–6 …

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.

The leptin system during human endometrial receptivity and preimplantation development.

The leptin system is implicated in the regulation of body weight and reproductive function, acting at endocrine and paracrine levels. This ligand-receptor system is mandatory for embryonic implantation in rodents. Here, we investigate the expression pattern of total leptin receptor (OB-R(T)), the long form (OB-R(L)) and short isoforms HuB219.1 and HuB219.3 in the human endometrium. Furthermore, we studied leptin and OB-R(T) mRNA during human embryonic preimplantation development and the embryonic regulation of the endometrial OB-R(L). Leptin receptor expression and its isoforms increase in the luteal phase and peak in the late part. Leptin receptor was localized at the epithelial and glandu…

Children born after autotransplantation of cryopreserved ovarian tissue. a review of 13 live births.

Abstract Introduction. Premature ovarian failure (POF) can occur naturally at an early age or be due to iatrogenic agents. Indeed, ovaries are very sensitive to cytotoxic treatment, especially to radiation and alkylating agents. Methods. Several options are currently available to preserve fertility in cancer patients and allow them to conceive when they have overcome their disease: embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation. Cryopreservation of ovarian tissue is the only option available for pre-pubertal girls and women who cannot delay the start of chemotherapy. Findings. Since the first live birth after autotransplantation of cryopreserved ovaria…

Evaluation of PAI-1 in endometriosis using a homologous immunocompetent mouse model

To analyze the role of PAI-1 (plasminogen activator inhibitor 1) in endometriotic lesion growth, we studied the effect of PAI-1 inhibition by PAI-039 using a homologous mouse model of endometriosis that allows noninvasive monitoring. Endometrial tissue from donor mice was collected, labeled with mCherry adenovirus, and implanted into a subcutaneous pocket on the ventral abdomen of recipient mice. Seven days after transplantation, mice were randomly allocated in two groups and treated once daily for 2 weeks with either vehicle (control group) or PAI-1 inhibitor (PAI-039 group). Endometriotic lesion size generated in recipient mice was monitored by mCherry signal. Animals were euthanized 21 d…

Inhibition of Delta-like 4 mediated signaling induces abortion in mice due to deregulation of decidual angiogenesis.

Objective: To explore whether the Dll4/Notch1 pathway plays a key role in regulating the vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) driven decidual angiogenesis and related pregnancy through induction of a tip/stalk phenotype. Methods: Progesterone-replaced ovariectomized pregnant mice received a single injection of YW152F (Dll4 blocking antibody, BAb) or placebo at embryonic day (E) 4.5. Animals were sacrificed at different time points; blood and uterus were collected for further analysis. Number of embryos and implantation site, uteri weight, and serum progesterone levels were assessed. Alterations in the tip/stalk phenotype were determined by quantitative immunofl…

Window of implantation transcriptomic stratification reveals different endometrial subsignatures associated with live birth and biochemical pregnancy

Objective To refine the endometrial window of implantation (WOI) transcriptomic signature by defining new subsignatures associated to live birth and biochemical pregnancy. Design Retrospective cohort study. Setting University-affiliated in vitro fertilization clinic and reproductive genetics laboratory. Patient(s) Healthy fertile oocyte donors (n = 79) and patients with infertility diagnosed by Endometrial Receptivity Analysis (n = 771). Intervention(s) None. Main Outcome Measure(s) WOI transcriptomic signatures associated with specific reproductive outcomes. Result(s) The retrospective cohort study was designed to perform a prediction model based on transcriptomic clusters for endometrial …

The Maternal Cytokine and Chemokine Profile of Naturally Conceived Gestations Is Mainly Preserved duringIn VitroFertilization and Egg Donation Pregnancies

This prospective longitudinal study aimed at comparing maternal immune response among naturally conceived (NC;n=25),in vitrofertilization (IVF;n=25), and egg donation (ED;n=25) pregnancies. The main outcome measures were, firstly, to follow up plasma levels of interleukin (IL) 1beta, IL2, IL4, IL5, IL6, IL8, IL10, IL17, interferon gamma, tumor necrosis factor-alpha (TNFα), transforming growth factor-beta (TGFβ), regulated upon activation normal T-cell expressed and secreted (RANTES), stromal cell-derived factor 1 alpha (SDF1α), and decidual granulocyte-macrophage colony-stimulating factor (GM-CSF) during the three trimesters of pregnancy during the three trimesters of pregnancy; secondly, t…

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 follicular hormonal profile in low-responder patients undergoing unstimulated cycles: is it hypoandrogenic?

STUDY QUESTION What is the final hormonal milieu of pre-ovulatory follicles of low-responder (LR) patients undergoing unstimulated cycles? SUMMARY ANSWER Neither androgen secretion nor LH was impaired in pre-ovulatory follicles of LR women. WHAT IS KNOWN ALREADY Therapies currently used to improve ovarian response in LR women have an impact on the final hormonal follicular milieu, and these changes are believed to be partially responsible for determining the success rate in these women. Surprisingly, as far as we know, there is no report of the final hormonal profile of LR women undergoing unstimulated cycles or evidence that follicular androgen secretion in LR women is impaired. STUDY DESI…

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…

Stem cell-secreted factor therapy regenerates the ovarian niche and rescues follicles.

Background Ovarian senescence is a normal age-associated phenomenon, but increasingly younger women are affected by diminished ovarian reserves or premature ovarian insufficiency. There is an urgent need for developing therapies to improve ovarian function in these patients. In this context, previous studies suggest that stem cell–secreted factors could have regenerative properties in the ovaries. Objective This study aimed to test the ability of various human plasma sources, enriched in stem cell–secreted factors, and the mechanisms behind their regenerative properties, to repair ovarian damage and to promote follicular development. Study Design In the first phase, the effects of human pla…

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

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 …

Vitrification of human oocytes.

In recent years, growing evidence for the safety and efficiency of oocyte vitrification has made this technique be increasingly proposed for fertility preservation (FP). The populations who could benefit from FP include oncological patients who need the option to preserve their gametes before undergoing potential sterilizing treatment, patients with non-oncologic conditions requiring gonadotoxic chemotherapy and women who wish to delay their motherhood for a variety of reasons. By vitrifying oocytes, women have the chance to conceive in the future, have their own genetic offspring and maintain their reproductive autonomy. This review focuses on describing current knowledge on oocyte vitrifi…

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 …

Influence of follicle rupture and uterine contractions on intrauterine insemination outcome: a new predictive model.

Objective To correlate the detection of follicle rupture and the number of uterine contractions per minute with the outcome of IUI and to build a predictive model for the outcome of IUI including these parameters. Design Retrospective cohort study. Setting Fertility clinic. Patient(s) We analyzed data from 610 women who underwent homologous or donor double IUI from 2005 to 2010 and whose data of uterine contractions or follicle rupture were recorded. Intervention(s) None. Main Outcome Measure(s) Live-birth rate. Result(s) Nine hundred seventy-nine IUI cycles were included. The detection of follicle rupture (odds ratio [OR], 1.98; 95% confidence interval [CI], 1.30–3.01) and the number of ut…

To invade, or to observe, that is the question

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…

A combined approach for gene discovery identifies insulin-like growth factor-binding protein-related protein 1 as a new gene implicated in human endometrial receptivity.

In the past, human endometrial receptivity has been investigated by chasing specific molecules throughout the menstrual cycle. Now the genomic approach allows us to investigate the hierarchical contribution of a high number of genes to a specific function. In this study, we analyzed differentially the gene expression pattern of 375 human cytokines, chemokines, and related factors, plus that of their receptors, in endometrial receptivity. To do this, we used a combined approach of human endometrium and cell lines. We have compared the gene expression pattern in receptive vs. prereceptive human endometria and contrasted the results with gene expression in the highly adhesive cell line (to JAR…

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

Undetectable viral RNA from SARS-CoV-2 in endometrial biopsies from women with COVID-19: a preliminary study.

The accuracy and reproducibility of the endometrial receptivity array is superior to histology as a diagnostic method for endometrial receptivity

Objective To compare the accuracy and reproducibility of the endometrial receptivity array (ERA) versus standard histologic methods. Design A comparative prospective study (May 2008–May 2012). Setting University-affiliated infertility clinic. Patient(s) Eighty-six healthy oocyte donors, regularly cycling, aged 20–34 years with a body mass index (BMI) of 19–25 kg/m 2 . Intervention(s) Endometrial biopsies were collected throughout the menstrual cycle. For the accuracy study, 79 samples were grouped into two cohorts: the training set (n = 79) for ERA machine-learning training and dating, and a dating subset (n = 49) for comparison between histologic and ERA dating. For the reproducibility stu…

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…

Stem cell paracrine actions in tissue regeneration and its potential therapeutic effect in human endometrium: a retrospective study.

Objective: Determining genetic and paracrine mechanisms behind endometrial regeneration in Asherman's Syndrome and Endometrial Atrophy (AS/EA) patients after autologous CD133+ bone marrow-derived stem cells (CD133+BMDSCs) transplantation. Design: Retrospective study using human endometrial biopsies and mouse models. Setting: Fundación-IVI, IIS-La Fe, Valencia, Spain. Samples: Endometrial biopsies collected before and after CD133+BMDSCs therapy, from 8 women with AS/EA (NCT02144987). And uterus from 5 mice, with only left horns receiving CD133+BMDSCs therapy. Methods: In human samples, hematoxylin and eosin (H&E) staining, RNA arrays, PCR validation and neutrophil elastase (NE) immunohistoch…

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…

Modeling Human Endometrial Decidualization from the Interaction between Proteome and Secretome

Context: Decidualization of the human endometrium, which involves morphological and biochemical modifications of the endometrial stromal cells (ESCs), is a prerequisite for adequate trophoblast invasion and placenta formation. Objective: This study aims to investigate the proteome and secretome of in vitro decidualized ESCs. These data were combined with published genomic information and integrated to model the human decidualization interactome. Design: Prospective experimental case–control study. Setting: A private research foundation. Patients: Sixteen healthy volunteer ovum donors. Intervention: Endometrial samples were obtained, and ESCs were isolated and decidualized in vitro. Main Ou…

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…

Failures (with some successes) of assisted reproduction and gamete donation programs

Although the possibilities for the treatment of infertility have been improved tremendously, not every couple will be treated successfully.Crude overall pregnancy rates of 50-65% per patient can be achieved nowadays, irrespective of the type of profertility treatment applied first.IVF only accounts for about 20% of the pregnancies achieved. Dropout is an important reason for not reaching the estimated pregnancy rate. Even after failed IVF, spontaneous pregnancies do occur. Sperm and oocyte donation (OD) offer additional chances to subfertile couples. Severity of the male factor (in sperm donation) and young donor age (in OD) are important determinants of success.Analysis of assisted reprodu…

Oocyte donation outcome after oncological treatment in cancer survivors.

Objective To study reproductive outcome in patients cured of cancer who required oocyte donation (OD) owing to iatrogenic ovarian dysfunction. Design Multicenter, unmatched, retrospective cohorts study. Setting Private, university-affiliated group of clinics. Patient(s) Women treated and cured of cancer (n = 142) who underwent 333 cycles of OD (exposed group) and women without a previous cancer diagnosis (n = 17,844) who underwent 29,778 cycles of OD (unexposed cohort) between January 2000 and January 2012. Intervention(s) Retrospective chart review. Main Outcome Measure(s) Pregnancy, implantation, miscarriage, and ongoing pregnancy rates. Result(s) There were no differences in terms of pre…

Proteomic analysis of extracellular vesicles secreted by primary human epithelial endometrial cells reveals key proteins related to embryo implantation

Abstract Background Successful implantation is dependent on coordination between maternal endometrium and embryo, and the role of EVs in the required cross-talk cell-to-cell has been recently established. In this regard, it has been reported that EVs secreted by the maternal endometrium can be internalized by human trophoblastic cells transferring their contents and enhancing their adhesive and invasive capacity. This is the first study to comprehensively evaluate three EV isolation methods on human endometrial epithelial cells in culture and to describe the proteomic content of EVs secreted by pHEECs from fertile women. Methods Ishikawa cells and pHEECs were in vitro cultured and hormonall…

Improving ovarian tissue cryopreservation for oncologic patients: slow freezing versus vitrification, effect of different procedures and devices.

Objective To compare slow freezing (SF) with four vitrification techniques (VT) for cryopreservation of ovarian tissue (OT) and to evaluate the best protocol for human OT in a xenograft model. Design Experimental study. Setting University hospital. Patient(s) Patients undergoing fertility preservation. Animal(s) Ovariectomized nude mice. Intervention(s) Cryopreservation of bovine OT after SF and four VTs (VT1, VT2, VT3, and VT4) by combining two cryoprotectant vitrification solutions (VS1 and VS2) and two devices (metallic grid and ethyl vinyl acetate bag), after which the cryopreservation of human OT by SF and VT1 and xenograft into nude mice. Main Outcome Measure(s) Follicular densities, …

Strategies for managing Asherman's syndrome and endometrial atrophy: Since the classical experimental models to the new bioengineering approach

Endometrial function is essential for embryo implantation and pregnancy, but managing endometrial thickness that is too thin to support pregnancy or an endometrium of compromised functionality due to intrauterine adhesions is an ongoing challenge in reproductive medicine. Here, we review current and emerging therapeutic and experimental options for endometrial regeneration with a focus on animal models used to study solutions for Asherman's syndrome and endometrial atrophy, which both involve a damaged endometrium. A review of existing literature was performed that confirmed the lack of consensus on endometrial therapeutic options, though promising new alternatives have emerged in recent ye…

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.

Effect of antiangiogenic treatment on peritoneal endometriosis-associated nerve fibers

Objective To investigate the effect of antiangiogenic treatment on experimental endometriotic lesion nerve fibers. Design Heterologous mouse model of endometriosis. Setting University Institute IVI, University Hospital La Fe. Animal(s) Ovariectomized nude mice (n = 16) receiving human endometrial fragments from oocyte donors (n = 4). Intervention(s) Endometrium fragments stuck in the peritoneum of 5-week-old female nude mice treated with vehicle (n = 8) and antiangiogenic agent cabergoline (n = 8; Cb 2, 0.05 mg/kg/day) for 14 days. Main Outcome Measure(s) Immunofluorescence analysis of von-Willebrand factor (vWF) and vascular smooth muscle cells (αSMA) for evaluating the number of immature …

The Italian law on assisted reproduction: a view from Spain

Despite the pessimistic concerns about the outcome of assisted reproduction in Italy after the application of the new law, initial reports show similar pregnancy rates. However, with increasing numbers, the deleterious effect of such a restrictive law will show up. Moreover, it may seriously affect the scientific production of Italian groups, which may be forced to migrate to other countries to maintain their independence and scientific freedom.

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…

The impact of next-generation sequencing technology on preimplantation genetic diagnosis and screening.

Largely because of efforts required to complete the Human Genome Project, DNA sequencing has undergone a steady transformation with still-ongoing developments of high-throughput sequencing machines for which the cost per reaction is falling drastically. Similarly, the fast-changing landscape of reproductive technologies has been improved by genetic approaches. Preimplantation genetic diagnosis and screening were established more than two decades ago for selecting genetically normal embryos to avoid inherited diseases and to give the highest potential to achieve stable pregnancies. Most recent additions to the IVF practices (blastocyst/trophectoderm biopsy, embryo vitrification) and adoption…

Disclosure of duplicative studies: damned if you don't

Duplicative publication requires duplicative editorializing. There are many forms of lesser redundancy such as unacknowledged secondary analyses of randomized clinical trials, fragmentation of studies with concurrent submission to various journals, and serial updating of observational studies. These practices result in publication bias. We have revised our instructions to authors to include disclosure of similar articles that are published, in press, or submitted to other journals to the editors upon submission.

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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…

SARS-CoV-2 infection risk assessment in the endometrium: viral infection-related gene expression across the menstrual cycle

Objective To determine the susceptibility of the endometrium to infection by—and thereby potential damage from—SARS-CoV-2. Design Analysis of SARS-Cov-2 infection-related gene expression from endometrial transcriptomic data sets. Setting Infertility research department affiliated with a public hospital. Patient(s) Gene expression data from five studies in 112 patients with normal endometrium collected throughout the menstrual cycle. Intervention(s) None. Main Outcome Measure(s) Gene expression and correlation between viral infectivity genes and age throughout the menstrual cycle. Result(s) Gene expression was high for TMPRSS4, CTSL, CTSB, FURIN, MX1, and BSG; medium for TMPRSS2; and low for…

Guidelines for biomarker discovery in endometrium: correcting for menstrual cycle bias reveals new genes associated with uterine disorders

Abstract Transcriptomic approaches are increasingly used in reproductive medicine to identify candidate endometrial biomarkers. However, it is known that endometrial progression in the molecular biology of the menstrual cycle is a main factor that could affect the discovery of disorder-related genes. Therefore, the aim of this study was to systematically review current practices for considering the menstrual cycle effect and to demonstrate its bias in the identification of potential biomarkers. From the 35 studies meeting the criteria, 31.43% did not register the menstrual cycle phase. We analysed the menstrual cycle effect in 11 papers (including 12 studies) from Gene Expression Omnibus: t…

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…

Evaluation of the antiproliferative, proapoptotic, and antiangiogenic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of leiomyoma.

Objective To assess the antiproliferative, proapoptotic, and antiangiogenic effects of the double-stranded RNA mimic polyinosine-polycytidylic acid (pIC) complexed with polyethylenimine [pIC PEI ] in xenografted human leiomyomas. Design Heterologous leiomyoma mouse model. Setting University-affiliated infertility center. Animal(s) Ovariectomized and hormone-replaced nude mice (n = 16) who received human leiomyoma fragment transplantation. Intervention(s) Leiomyoma fragments placed in the peritoneum of 5-week-old nude female mice and treated with the vehicle (n = 8) or 0.6 mg/kg [pIC PEI ] (n = 8) for 4 weeks. Main Outcome Measure(s) The size of the leiomyoma implants, and cellular prolifera…

Mitochondrial DNA content decreases during in vitro human embryo development: insights into mitochondrial DNA variation in preimplantation embryos donated for research.

Objective To assess the mitochondrial DNA (mtDNA) load and variation in human oocytes and during preimplantation embryo development using specimens donated for research. Design Prospective cohort study. Setting Not applicable. Patients A total of 50 in vitro fertilization patients and 11 oocyte donors whose specimens were obtained between July 2017 and July 2018. Interventions None. Main Outcome Measures All specimens were separately collected. Quantitative polymerase chain reaction was performed with SurePlex DNA Amplification System (Illumina). Primers for the adenosine triphosphate 8 mitochondrial gene and the β-actin were used. Data were statistically analyzed by analysis of variance wi…

Ovarian stimulation for ovulation induction and in vitro fertilization in patients with systemic lupus erythematosus and antiphospholipid syndrome.

Objective To review the current evidence regarding the relationship between systemic lupus erythematosus (SLE) and antiphospholipid syndrome and female infertility, as well as the risks associated with ovarian stimulation for ovulation induction and IVF. To establish, based on this information, guidelines for safe and successful assisted reproductive technology (ART). Design A MEDLINE computer search was performed to identify relevant articles. Result(s) Systemic lupus erythematosus and antiphospholipid syndrome are not related to infertility, except for cases of amenorrhea accompanying severe flares, renal insufficiency-related hypofertility, and ovarian failure secondary to cyclophosphami…

CXCL10 and IL-6 induce chemotaxis in human trophoblast cell lines.

The investigation of trophoblast chemoattractive molecules in humans is of high interest for the reproductive field. Current evidence in ruminants demonstrates that CXCL10, formerly the interferon-gamma-inducible protein 10 (IP-10), is a potent chemotactic molecule implicated in the migration of trophoblast cells during early gestation. The aim of this work was to explore the existence of CXCL10/CXCR3 in the human model. Furthermore, chemotaxis assays were performed to demonstrate CXCL10 chemotactic activity in the human trophoblast cell lines JEG-3 and AC-1M88. Surprisingly, the conditioned media from epithelial endometrial cells (EEC) induced the highest trophoblast migration rate. Cytoki…

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…

Day-3 embryo metabolomics in the spent culture media is altered in obese women undergoing in vitro fertilization

Objective To determine whether the global metabolomic profile of the spent culture media (SCM) of day-3 embryos is different in obese and normoweight women undergoing in vitro fertilization (IVF). Design Prospective cohort analysis. Setting IVF clinic. Patient(s) Twenty-eight young, nonsmoking women with normoweight, nonsmoking male partners with mild/normal sperm factors undergoing a first IVF attempt for idiopathic infertility, tubal factor infertility, or failed ovulation induction: obese ovulatory women (n = 12); obese women with polycystic ovary syndrome (PCOS; n=4); normoweight ovulatory women (n = 12). Intervention(s) Fifty μl of SCM collected from two day-3 embryos of each cohort. M…

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…

Serum interleukin-6 levels are elevated in women with minimal-mild endometriosis.

BACKGROUND: There is a need for a reliable marker of endometriosis, especially in early stages of peritoneal disease during which imaging is not effective. The use of serum interleukin (IL)-6 as a marker is controversial. To readdress the matter, patients undergoing laparoscopy were prospectively evaluated for serum IL-6 levels. MATERIALS AND METHODS: A total of 119 women 31 years old who underwent laparoscopy were divided into groups: control patients (n = 38) with no pathologic findings; endometriosis sufferers (n = 47) with minimal-mild (MM, n = 11) or moderate-severe (MS, n = 36) endometriosis; uterine myomas (n = 13) and benign ovarian pathologies (n = 21). Blood was drawn on cycles da…

cGMP MODULATES STEM CELLS DIFFERENTIATION TO NEURONS IN BRAIN IN VIVO

During brain development neural stem cells may differentiate to neurons or to other cell types. The aim of this work was to assess the role of cGMP (cyclic GMP) in the modulation of differentiation of neural stem cells to neurons or non-neuronal cells. cGMP in brain of fetuses was reduced to 46% of controls by treating pregnant rats with nitroarginine-methylester (L-NAME) and was restored by co-treatment with sildenafil.Reducing cGMP during brain development leads to reduced differentiation of stem cells to neurons and increased differentiation to non-neuronal cells. The number of neurons in the prefrontal cortex originated from stem cells proliferating on gestational day 14 was 715 +/- 14/…

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 …

Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expressio…

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…

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…

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…

Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications

[Abstract] BACKGROUND: Ectopic pregnancy is a life-threatening condition for which novel screening tools that would enable early accurate diagnosis would improve clinical outcomes. Kisspeptins, encoded by KISS1, play an essential role in human reproduction, at least partially by regulating placental function and possibly embryo implantation. Kisspeptin levels are elevated massively in normal pregnancy and reportedly altered in various gestational pathologic diseases. Yet, the pathophysiologic role of KISS1/kisspeptin in ectopic pregnancy has not been investigated previously. OBJECTIVE: The purpose of this study was to evaluate changes of KISS1/kisspeptin levels in ectopic pregnancy and thei…

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

Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis

Elevated serum progesterone levels at the end of the follicular phase in controlled ovarian stimulation (COS) leads to a poorer ongoing pregnancy rate in IVF cycles due to reduced endometrial receptivity. The objective of this study was to use microarray technology to compare endometrial gene expression profiles at the window of implantation according to the levels of circulating progesterone.For this prospective cohort study, microarray data were obtained from endometrial biopsies from 12 young healthy oocyte donors undergoing COS with pituitary suppression by either gonadotrophin-releasing hormone (GnRH) agonists or antagonists, and recombinant FSH. On the day of recombinant chorionic gon…

Embryonic adhesion is not affected by endometrial leptin receptor gene silencing.

Objective In rodents, evidence suggests that the leptin system is mandatory for embryonic implantation. We aimed to investigate the functional relevance of the endometrial leptin receptor (OB-R) in the adhesion phase of human implantation. Design We used an in vitro model for embryonic adhesion, composed of a human endometrial cell line (HEC1-A) and B6C3F1 mouse embryos. The OB-R gene was silenced in a stable manner by RNA interference, and embryonic adhesion rates were analyzed. Setting Research laboratory at a university-affiliated center. Intervention(s) RNA interference. Main Outcome Measure(s) Embryonic adhesion in cells treated with OB-R RNAi. Result(s) The OB-R shRNA-transfected cell…

Improved Models of Human Endometrial Organoids Based on Hydrogels from Decellularized Endometrium

Organoids are three-dimensional (3D) multicellular tissue models that mimic their corresponding in vivo tissue. Successful efforts have derived organoids from primary tissues such as intestine, liver, and pancreas. For human uterine endometrium, the recent generation of 3D structures from primary endometrial cells is inspiring new studies of this important tissue using precise preclinical models. To improve on these 3D models, we decellularized pig endometrium containing tissue-specific extracellular matrix and generated a hydrogel (EndoECM). Next, we derived three lines of human endometrial organoids and cultured them in optimal and suboptimal culture expansion media with or without EndoEC…

Reprogrammed induced pluripotent stem cells: how suitable could they be in reproductive medicine?

Human embryonic stem cells have the greatest potential for regenerative and reproductive medicine; unfortunately, their full application is limited by ethical and technical problems. In order to overcome these problems and get patient specific pluripotent cells from somatic cells, the field of reprogramming has moved to the generation of induced pluripotent stem cells by overexpression of four transcription factors after viral infection of the patient's somatic cells. In the present paper we review the limitations and milestones of this technique in both regenerative and reproductive medicine.

O-142 COVID19-free endometrium: Undetectable viral RNA in endometrial biopsies from positive symptomatic SARS-CoV-2 women

Abstract Study question Does SARS-CoV-2 infect the endometrial tissue in women with coronavirus disease 2019 (COVID-19)? Summary answer Symptomatic women with COVID-19 report no presence, in the short term, of viral RNA from SARS-CoV-2 in the endometrium. What is known already The recent emergence of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has not allowed yet to establish putative relations between this disorder and other existing pathologies. It is the case with fertility problems and the reproductive organs, including a possible endometrial disorder caused by the virus. Thus, an important step is to elucidate the viral presence in different hu…

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 …

Better together than alone: the cumulus benefits.

A Natural Xenogeneic Endometrial Extracellular Matrix Hydrogel Toward Improving Current Human in vitro Models and Future in vivo Applications

Decellularization techniques support the creation of biocompatible extracellular matrix hydrogels, providing tissue-specific environments for both in vitro cell culture and in vivo tissue regeneration. We obtained endometrium derived from porcine decellularized uteri to create endometrial extracellular matrix (EndoECM) hydrogels. After decellularization and detergent removal, we investigated the physicochemical features of the EndoECM, including gelation kinetics, ultrastructure, and proteomic profile. The matrisome showed conservation of structural and tissue-specific components with low amounts of immunoreactive molecules. EndoECM supported in vitro culture of human endometrial cells in t…

DEVELOPMENT OF SECRETOR AND GESTATIONAL PATIENT-DERIVED ORGANOIDS FROM ADENOMYOSIS DISEASE AS AN IN VITRO MODEL TO STUDY ADENOMYOSIS-RELATED INFERTILITY AND PERSONALIZED DRUG SCREENING

Vitamin D as an effective treatment in human uterine leiomyomas independent of mediator complex subunit 12 mutation.

Objective To study whether vitamin D (VitD) inhibits cell proliferation and Wnt/β-catenin and transforming growth factor−β (TGFβ) signaling pathways in uterine leiomyomas independent of mediator complex subunit 12 (MED12) mutation status. Design Prospective study comparing leiomyoma vs. myometrial tissues and human uterine leiomyoma primary (HULP) cells treated with or without VitD and analyzed by MED12 mutation status. Setting Hospital and university laboratories. Patient(s) Women with uterine leiomyoma without any treatment (n = 37). Intervention(s) Uterine leiomyoma and myometrium samples were collected from women undergoing surgery because of symptomatic leiomyoma pathology. Main Outcom…

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…

Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) as a putative human endometrial stem cell marker†

The endometrium is recognized for its remarkable regenerative and remodeling capacity. Every month this hormonally regu- lated organ undergoes cycles of growth (from 0.5-2 to 7 mm), regression and shedding of two-third of the tissue, leading to its monthly renewal that occurs � 400 times in a woman's reproductive lifetime. Several groups have suggested the existence of a human endometrial somatic stem cell (SSC) population located around the spiral arterioles of the basalis. Different groups have isolated, identified and charac- terized putative endometrial SSC populations in human endometrium based on the general features of undifferentiated cells, such as slow cycling detected using the 5…

Inter-cycle and inter-observer variability of the antral follicle count in routine clinical practice

Antral follicle count (AFC) is a reliable predictor of ovarian response to stimulation and its inter-cycle and inter-observer variability has been extensively studied on in vitro fertilization (IVF), mostly in highly selected populations within studies not originally designed for this purpose. In this retrospective cohort study, we assess the inter-cycle variation of AFC in a setting similar to that of the daily practice. We included only patients undergoing mild stimulation for intrauterine insemination (IUI). One hundred and forty-eight patients had two (62 patients, group A), three (49 patients, group B) or four (37 patients, group C) IUI cycles and AFC was measured on early follicular p…

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.

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…

Single-cell RNA sequencing of oocytes from ovarian endometriosis patients reveals a differential transcriptomic profile associated with lower quality

Abstract STUDY QUESTION Do oocytes from women with ovarian endometriosis (OE) have a different transcriptomic profile than those from healthy women? SUMMARY ANSWER Oocytes from endometriosis patients, independently of whether they came from the affected ovary, exhibited a differential transcriptomic profile compared to oocytes from healthy egg donors. WHAT IS KNOWN ALREADY Studies of endometriosis have sought to determine whether OE affects oocyte quality. While many reports indicate that oocytes recovered from endometriotic ovaries may be affected by the disease, other studies have found no significant differences among oocyte/embryo quality and fertilization, implantation and pregnancy ra…

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% …

Early pregnancy loss in women stimulated with gonadotropin-releasing hormone antagonist protocols according to oral contraceptive pill pretreatment.

Objective To evaluate and compare the risk of early pregnancy loss in patients stimulated with GnRH antagonist protocols according to oral contraceptive pill (OCP) pretreatment. Design Retrospective case–control study. Setting Instituto Valenciano de Infertilidad. University of Valencia. Spain. Patient(s) One thousand five hundred thirty-nine patients, aged Intervention(s) Reproductive outcome was compared based on the application (or not) of OCP pretreatment: 944 women were included in the OCP group and 595 in the non-OCP group. The Student's t test was used for statistics. Main Outcome Measure(s) Pregnancy, biochemical pregnancy, ectopic pregnancy, early clinical pregnancy loss, early pre…

Sildenafil citrate improves perinatal outcome in fetuses from pre-eclamptic rats

Please cite this paper as: Herraiz S, Pellicer B., Serra V, Cauli O, Cortijo J, Felipo V, Pellicer A. Sildenafil citrate improves perinatal outcome in fetuses from pre-eclamptic rats. BJOG 2012;119:1394–1402. Objective  To evaluate perinatal outcome after sildenafil citrate (SC) administration at the onset of pregnancy in a rat pre-eclampsia model. Design  In vivo animal experimental study. Setting  Fundacion IVI-Instituto Universitario IVI, Valencia, Spain. Sample Control and pre-eclampsia-induced pregnant Wistar rats exposed to chronic SC administration. Methods  We evaluated the use of SC, which was tested as a potential therapeutic tool to maintain vasodilatation in complicated pregnanc…

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 …

OC005: Ultrasound bioeffects: Quantification of cellular damage in animal fetal liver after use of Doppler pulse to measure ductus venosus

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…

Implantation is apparently unaffected by the dopamine agonist Cabergoline when administered to prevent ovarian hyperstimulation syndrome in women undergoing assisted reproduction treatment: a pilot study

Background Ovarian hyperstimulation syndrome (OHSS) is a result of ovarian overexpression of vascular endothelial growth factor (VEGF) and its receptor 2 (VEGFR2). VEGF/VEGFR2 binding disrupts cellular junctions and increases vascular permeability (VP), a characteristic of OHSS, but enhances angiogenesis, which is a fundamental step in implantation. In animals, the dopamine agonist Cabergoline (Cb2) prevents VP without affecting angiogenesis. In humans, Cb2 averts OHSS, but a possible detrimental effect on angiogenesis and implantation has not been explored. A pilot study was designed to analyze whether or not Cb2 administration, as a procedure for preventing OHSS, affects the outcome of as…

Blood group and ovarian hyperstimulation syndrome.

Blood group does not constitute a risk factor for the onset of the early form of ovarian hyperstimulation syndrome in women "at risk."

Transcriptomic behavior of genes associated with chromosome 21 aneuploidies in early embryo development.

To analyze how chromosome 21 (HSA21) ploidy affects global gene expression of early human blastocysts.Prospective study.University-affiliated in vitro fertilization clinic.A total of 26 high-quality donated embryos from in vitro fertilization (IVF) patients: trisomy 21 (n = 8), monosomy 21 (n = 10), and euploid (n = 8) blastocysts.None.Blastocyst transcriptome changes and its associated functions.Trisomy 21, monosomy 21, and euploid blastocysts were classified by comparative genomic hybridization. The global transcriptome of whole blastocysts was analyzed with small cell number RNA sequencing, and they were compared to understand the gene expression behavior at early development and its imp…

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 …

Moderate ovarian stimulation does not increase the incidence of human embryo chromosomal abnormalities in in vitro fertilization cycles.

A high chromosomal abnormalities rate has been observed in human embryos derived from in vitro fertilization (IVF) treatments. The real incidence in natural cycles has been poorly studied, so whether this frequency may be induced by external factors, such as use of gonadotropins for ovarian stimulation, remains unknown.We conducted a prospective cohort study in a University-affiliated private infertility clinic with a comparison between unstimulated and stimulated ovarian cycles in the same women. Preimplantation genetic screening by fluorescence in situ hybridization was performed in all viable d 3 embryos.The primary objective was to compare the incidence of embryo chromosomal abnormaliti…

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

Timing does not influence outcomes in double intrauterine insemination

Uterine disorders affecting female fertility: what are the molecular functions altered in endometrium?

[EN]: Objective:To determine the molecular functions of genes exhibiting altered expression in the endometrium of women with uterine disorders affecting fertility. Design: Retrospective analysis integrating case and control data from multiple cohorts with endometrium gene expression in women with uterine disorders. Setting: Infertility research department affiliated with a university hospital. Patient(s): Two hundred and forty women, 121 of whom were controls, 119 of whom had endometrial adenocarcinoma (ADC), recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or stage II–IV endometriosis. Intervention(s): None. Main Outcome Measure(s): Genomewide gene expression and alter…

TREATMENT WITH SILDENAFIL PREVENTS IMPAIRMENT OF LEARNING IN RATS BORN TO PRE-ECLAMPTIC MOTHERS

Pre-eclampsia is an important hypertensive pregnancy disorder and a main cause of maternal and fetal morbidity and mortality Children born from mothers with preeclampsia may present cognitive deficits The mechanisms leading to this cognitive impairment remain unclear and no treatments to improve it have been tested Pre-eclampsia is associated with impaired regulation of the nitric oxide 3 5 guanosine monophosphate cyclic (cGMP) pathway, which modulates some cognitive functions We hypothesized that alterations in the NO-cGMP pathway would be involved in the mechanisms leading to cognitive impairment in rats born to pre-eclamptic mothers and that treatment with sildenafil an inhibitor of the …

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…

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

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.

Polycystic ovarian syndrome: assessment with color Doppler angiography and three-dimensional ultrasonography.

We conducted a three-dimensional ultrasonographic evaluation of the size and structure of the ovaries of women who had clinical and biochemical findings suggestive of polycystic ovary syndrome. We carried out a comparative color Doppler frequency and color Doppler amplitude study of the vascular patterns of these ovaries. This study involved 65 women of reproductive age with polycystic ovary syndrome and 25 eumenorrheic women who were not taking hormonal contraceptives and who had a body mass index below 25 kg/m2. Compared to controls, women with polycystic ovary syndrome had larger ovaries and thicker stroma, increased impedance in the uterine arteries, increased stromal vascularity with d…

Evidence-based medicine is gaining momentum

Controlled Ovarian Stimulation Induces a Functional Genomic Delay of the Endometrium with Potential Clinical Implications

Context: Controlled ovarian stimulation induces morphological, biochemical, and functional genomic modifications of the human endometrium during the window of implantation. Objective: Our objective was to compare the gene expression profile of the human endometrium in natural vs. controlled ovarian stimulation cycles throughout the early-mid secretory transition using microarray technology. Method: Microarray data from 49 endometrial biopsies obtained from LH+1 to LH+9 (n = 25) in natural cycles and from human chorionic gonadotropin (hCG) +1 to hCG+9 in controlled ovarian stimulation cycles (n = 24) were analyzed using different methods, such as clustering, profiling of biological processes…

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…

Similar endometrial development in oocyte donors treated with either high- or standard-dose GnRH antagonist compared to treatment with a GnRH agonist or in natural cycles.

Background This descriptive study evaluates the impact on endometrial development of standard and high doses of a GnRH antagonist in stimulated cycles compared with GnRH agonist and natural cycles. Methods Thirty-one oocyte donors were treated with a combination of rFSH and 0.25 mg/day ganirelix (standard dose), 2 mg/day ganirelix (high dose) or 0.6 mg/day buserelin (long protocol). Vaginal progesterone (200 mg/day) was administered in the luteal phase. Endometrial biopsies were performed 2 and 7 days after HCG administration. Additional biopsies were carried out in a subset of 12 subjects, 2 and 7 days following the LH peak of their previous natural cycle. Biopsies were evaluated histologi…

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…

A minimally invasive methodology based on morphometric parameters for day 2 embryo quality assessment.

[EN] The risk of multiple pregnancy to maternal fetal health can be minimized by reducing the number of embryos transferred. New tools for selecting embryos with the highest implantation potential should be developed. The aim of this study was to evaluate the ability of morphological and morphometric variables to predict implantation by analysing images of embryos. This was a retrospective study of 135 embryo photographs from 112 IVF ICSI cycles carried out between January and March 2011. The embryos were photographed immediately before transfer using Cronus 3 software. Their images were analysed using the public program ImageJ. Significant effects (P < 0.05), and higher discriminant power …

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 (…

Dopamine agonist administration causes a reduction in endometrial implants through modulation of angiogenesis in experimentally induced endometriosis

Survival of newly implanted retrograde-shed endometrial tissue during menstruation in an ectopic location requires an adequate blood supply. This suggests that angiogenesis is a prerequisite for the development of endometriosis and that its inhibition may be a target for preventing development. Previous studies have shown that vascular endothelial growth factor (VEGF), a heparin-binding glycoprotein, has an essential role in angiogenesis. The main regulatory factor for angiogenesis appears to be binding of VEGF to its type-2 receptor (VEGFR-2). Cabergoline (Cb2) and other dopamine agonists promote endocytosis of the VEGF receptor-2 (VEGFR-2) in endothelial cells, thereby preventing VEGF-VEG…

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…

Novel therapeutic targets to improve IVF outcomes in endometriosis patients: a review and future prospects

AbstractBACKGROUNDPatients with endometriosis often experience infertility and have poor IVF outcomes, with low fertilization and pregnancy rates. Although many theories have tried to explain the mechanisms underlying infertility in these patients, none of them is conclusive.OBJECTIVE AND RATIONALEIn this review, we discuss the pathologic mechanisms through which endometriosis likely leads to infertility along with the therapeutic options used to date to treat endometriosis-related infertility and, thereby, to improve IVF outcomes in patients with endometriosis.SEARCH METHODSWe performed a comprehensive literature search of clinical outcomes in endometriosis and the molecular mechanisms con…

High-dose recombinant LH add-back strategy using high-dose GnRH antagonist is an innovative protocol compared with standard GnRH antagonist.

High daily doses of gonadotrophin-releasing hormone (GnRH) antagonists during the follicular phase of ovarian stimulation were associated with low implantation rates. To test if this occurred because of profound pituitary suppression, the pituitary response was suppressed with a high-dose GnRH antagonist and recombinant LH (rLH) was added back to correct the implantation rate. An open-label, randomized, controlled, prospective clinical study in 60 patients undergoing IVF was performed. GnRH antagonist was initiated on day 6 of stimulation (2 mg/day) together with 375 IU rLH, and maintained until the day of HCG administration. Controls received 0.25 mg/day GnRH antagonist. Fluctuating LH con…

Planes de recuperación de flora amenazada de la comunidad valenciana. Resultados tras tres años de la aprobación de la normativa legal

The Valencian Community (Spain) holds three plant species (Cistus heterophyllus Desf., Limonium perplexum L. Sáez & Rosselló and Silene hifacensis Rouy ex Willk.) listed into the category In danger of extinction, for which there is a joint Recovery Plan passed by the Valencian Government through the Order 1/2015, January 8, of the Department of Infrastructures, Land and Environment. Among the aims of this Recovery Plan, to improve the conservation status of these species in the Valencian territory, provisions of its Article 3 are highlighted. This article specifies that they population values that justify their passage of the category In danger of extinction to Vulnerable must be reached. T…

Activin and inhibin A in predicting outcome of pregnancies of unknown location after ART

Abstract The aim was to investigate the predictive value of a single serum determination of activin A and inhibin A for classifying pregnancies of unknown location (PUL) after IVF cycles in both own fresh and donated oocytes. A case–control study conducted in a University-affiliated IVF center. Pregnancy outcomes after own fresh oocytes included 12 failing PUL, 12 ectopic pregnancies (EP) and a control group of 24 singleton intrauterine pregnancies (IUP). The same scheme was followed for the oocyte donation recipients. Inhibin A, activin A, β-hCG and Progesterone (P) were determined. In the own fresh oocytes IVF, the AUC for predicting EP vs. f failing PUL were: Activin A: 0.458 and Inhibin…

Derivation and characterization of three new Spanish human embryonic stem cell lines (VAL −3 −4 −5) on human feeder and in serum-free conditions

A total of 184 human embryos, frozen for >5 years, were donated; informed consent was obtained according to Spanish law 45/2003. Survival rate was 40% and three out of 24 blastocysts (12.5%) developed into putative hESC lines, named VAL-3, VAL-4, and VAL-5. The derivation process was performed on microbiologically tested and irradiated human foreskin fibroblasts and designed to minimize contact with xeno-components in knockout DMEM supplemented with knockout serum replacement, and basic fibroblast growth factor. Fingerprinting and HLA typing of the cell lines allowed their identification and traceability. Karyotype was normal for VAL-3 (46XY), VAL-4 (46XX) and VAL-5 (46XX). All three hESC l…

Maternal serum ghrelin levels in early IVF pregnancies: lack of prognostic value for viable pregnancy and altered post-prandial responses

Background Ghrelin is a pleiotropic hormone, involved in the control of growth and metabolism, whose circulating levels fluctuate in relation to food intake and body mass index. Ghrelin has been detected in the decidualized endometrium, as well as in human and rat placenta. Methods A total of 106 patients undergoing IVF procedures were prospectively recruited. On Days 16 and 23 after oocyte retrieval, the patients were subjected to blood sampling after overnight fasting, for determination of serum ghrelin, hCGbeta and progesterone levels. In addition, ghrelin levels were assayed in these groups, 2 h after ingestion of a fixed-calorie meal. Results The subjects were divided according to whet…

Embryologic outcome and secretome profile of implanted blastocysts obtained after coculture in human endometrial epithelial cells versus the sequential system.

Objective To compare embryologic and clinical outcomes in terms of preimplantation development, implantation, pregnancy rates, and secretome profile of implanted blastocysts from the preimplantation genetic diagnosis program grown in sequential versus endometrial epithelial cell (EEC) coculture system. Design Retrospective clinical study and prospective experimental study. Setting In vitro fertilization clinical unit and university research laboratory. Intervention(s) Blastomere biopsy, embryo culture, blastocyst transfer, and protein analysis of the media conditioned from implanted embryos obtained from coculture and sequential systems. Main Outcome Measure(s) Clinical study: blastocyst, i…

Prenatal Brain Damage in Preeclamptic Animal Model Induced by Gestational Nitric Oxide Synthase Inhibition

Cerebral palsy is a major neonatal handicap with unknown aetiology. There is evidence that prenatal brain injury is the leading cause of CP. Severe placental pathology accounts for a high percentage of cases. Several factors predispose to prenatal brain damage but when and how they act is unclear. The aim of this paper was to determine if hypoxia during pregnancy leads to damage in fetal brain and to evaluate the localization of this injury. An animal model of chronic hypoxia produced by chronic administration of a nitric oxide synthase inhibitor (L-NAME) was used to evaluate apoptotic activity in fetal brains and to localize the most sensitive areas. L-NAME reproduces a preeclamptic-like c…

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 …

Ultrasound bioeffects in rats: quantification of cellular damage in the fetal liver after pulsed Doppler imaging

Objective To determine whether pulsed Doppler examination of the ductus venosus in rat fetuses could damage exposed tissue. Methods On gestational day 18, the livers of a mean of approximately five fetuses per mother (n = 5.14, SD = 1.6), in a cohort of 35 pregnant female rats, were exposed individually to pulsed Doppler and these were considered the 'exposed group'. The remaining fetuses in each pregnant rat (n = 5.16, SD = 2.1) formed the 'control group'. We tested for 600, 300, 60, 20, 15, 10 and 3 s of exposure of the fetal ductus venosus and the damage was evaluated measuring a cell death index of apoptotic activity at 7 h post-exposure (n = 16). In addition, subgroups of mothers were …

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,…

Comparison of different sources of platelet-rich plasma as treatment option for infertility-causing endometrial pathologies

Objective To study the effect of human plasma from different sources, namely, umbilical cord blood and adult blood platelet-rich plasma (PRP), on the regeneration of endometrial damage. Design Composition analysis, in vitro approaches, and a preclinical murine model using plasma to promote endometrial regeneration. Setting Hospital and university laboratories. Patient(s)/Animal(s) Adult plasma from four Asherman syndrome/endometrial atrophy patients and one fertile woman, commercial umbilical cord plasma, and uterine-damaged NOD/SCID mice model were used. Intervention(s) Endometrial stromal cells from primary culture and an endometrial stem cell line were cultured in vitro, and uterine-dama…

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…

Transcriptional changes through menstrual cycle reveal a global transcriptional derepression underlying the molecular mechanism involved in the window of implantation

The human endometrium is a dynamic tissue that only is receptive to host the embryo during a brief time in the middle secretory phase, called the window of implantation (WOI). Despite its importance, regulation of the menstrual cycle remains incompletely understood. The aim of this study was to characterize the gene cooperation and regulation of menstrual cycle progression, to dissect the molecular complexity underlying acquisition of endometrial receptivity for a successful pregnancy, and to provide the scientific community with detailed gene co-expression information throughout the menstrual cycle on a user-friendly web-tool database. A retrospective gene co-expression analysis was perfor…

Human Endometrial Side Population Cells Exhibit Genotypic, Phenotypic and Functional Features of Somatic Stem Cells

During reproductive life, the human endometrium undergoes around 480 cycles of growth, breakdown and regeneration should pregnancy not be achieved. This outstanding regenerative capacity is the basis for women's cycling and its dysfunction may be involved in the etiology of pathological disorders. Therefore, the human endometrial tissue must rely on a remarkable endometrial somatic stem cells (SSC) population. Here we explore the hypothesis that human endometrial side population (SP) cells correspond to somatic stem cells. We isolated, identified and characterized the SP corresponding to the stromal and epithelial compartments using endometrial SP genes signature, immunophenotyping and char…

Hormonal and molecular characterization of follicular fluid, cumulus cells and oocytes from pre-ovulatory follicles in stimulated and unstimulated cycles

background: The use of ovarian stimulation, to stimulate a multi-follicular response for assisted reproduction treatments, may force the production of oocytes from follicles that do not reach optimal maturation, possibly yielding oocytes that are not fully competent. The present study aimed to define the follicular environment and oocyte competence of unstimulated pre-ovulatory follicles, to compare it with that of similar-sized stimulated follicles. For this purpose, we analyzed the follicular hormonal milieu, the oocyte meiotic spindle, the embryo development and the cumulus cells gene expression (GE) profiles. methods and results: The study population was divided in two groups: (i) 42 oo…

The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis

Implantation of a retrogradely shed endometrium during menstruation requires an adequate blood supply, which allows the growth of endometriotic lesions. This suggests that the development of endometriosis can be impaired by inhibiting angiogenesis. The growth of endometriotic foci is impaired by commercial oncological antiangiogenic drugs used to block vascular endothelial growth factor (VEGF) signaling. The dopamine agonist cabergoline (Cb2) inhibits the growth of established endometriosis lesions by exerting antiangiogenic effects through VEGFR2 inactivation. However, the use of ergot-derived Cb2 is associated with an increased incidence of cardiac valve regurgitation. To evaluate the pot…

Adjuncts for ovarian stimulation: when do we adopt “orphan indications” for approved drugs?

Several drugs, shown to be safe for other uses, have proven to be highly effective adjuncts for ovarian stimulation. The authors evaluate these "orphan" indications and make recommendations so that more patients will benefit from their use.

Fresh Human Orthotopic Ovarian Cortex Transplantation: Long-term Results

An increasing number of young women are being diagnosed with cancer, and most cancer treatments have irreversibly negative effects on reproduction. Ovarian stimulation and preservation of oocytes or embryos is far from an ideal solution, in part because hormonal treatment may adversely affect some cancers. Another possibility is cryopreservation of ovarian tissue for later autotransplantation, but the ischemic damage caused by the procedure can lead to follicle loss. Using the ovarian medulla for orthotopic ovarian cortex transplantation might limit the risk of ischemia because the ovarian artery would assure a good blood supply. In addition, the medulla may have a role in follicular develo…

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.

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…

Uterine Receptivity and the Ramifications of Ovarian Stimulation on Endometrial Function

Controlled ovarian stimulation (COS) is widely used in assisted reproduction techniques (ART). However, hormonal treatment induces endometrial alterations that may alter implantation rates compared with natural cycles. Endometrial alterations have been observed by histological and biochemical techniques. The recent developments in functional genomics have provided objective tools to analyze the endometrium in natural cycles and evaluate the impact of COS protocols in endometrial development. This article describes the fundamental aspects of endometrial receptivity in natural cycles and reports how COS affects the morphology, biochemistry, and the genomic pattern of the endometrium.

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

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…

Female overweight is not associated with a higher embryo euploidy rate in first trimester miscarriages karyotyped by hysteroembryoscopy.

Overweight women (body mass index ≥ 25 kg/m(2)) present an embryo euploidy rate in first trimester miscarriages similar to normoweight controls after a selective biopsy and karyotyping of embryo and/or chorion samples taken by hysteroembryoscopy.

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 …

Haemodynamic effects of long-term administration of sildenafil in normotensive pregnant and non-pregnant rats

Please cite this paper as: Pellicer B, Herraiz S, Cauli O, Rodrigo R, Asensi M, Cortijo J, Serra V, Morcillo E, Felipo V, Simon C, Pellicer A. Haemodynamic effects of long-term administration of sildenafil in normotensive pregnant and non-pregnant rats. BJOG 2011;118:615–623. Objective  To determine the effects of chronic administration of sildenafil citrateon healthy pregnant rats. Design In vivo animal experimental study. Setting  Fundacion IVI–Instituto Universitario IVI, Valencia, Spain. Sample  Pregnant and non-pregnant Wistarrats exposed to chronic administration of sildenafil. Methods  Placental cross-barrier and feto-maternal relationship levels, maternal blood pressure, and haemody…

In vitro fertilization with personalized blastocyst transfer versus frozen or fresh blastocyst transfer: a multicenter, randomized clinical trial

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…

Twins born after transplantation of ovarian cortical tissue and oocyte vitrification

Objective To present a combination of ovarian tissue and oocyte cryopreservation as an effective strategy for achieving pregnancy in a breast cancer patient. Design Case report. Setting Tertiary care university-affiliated hospital, tissue bank, and infertility clinic. Patient(s) A 36-year-old patient diagnosed with atypical medullar breast cancer and negative for estrogen, P, and HER2 receptors underwent ovarian tissue cryopreservation before receiving chemotherapy and radiotherapy. Intervention(s) Laparoscopic ovarian cortex extraction, ovarian tissue cryopreservation, ovarian tissue thawing and transplantation, controlled ovarian stimulation (COS), oocyte retrieval, vitrification and IVF,…

Improved effectiveness from individualized dosing of self-administered biologics for the treatment of moderate-to-severe psoriasis: a 5-year retrospective chart review from a Spanish University Hospital

Background: Biologics for moderate-to-severe psoriasis are expensive and treatment substitutions may vastly increase cost. Moreover, administration regimens in routine practice may differ from recommended guidelines. Objectives: To evaluate long-term effectiveness, regimen, drug-survival, and efficiency of self-administered biologics in clinical practice. Methods: We performed a 5-year retrospective study in 72 patients (44 ± 14 years old) with moderate-to-severe psoriasis at the University Hospital La Plana (Vila-real, Spain), treated with subcutaneous biologics. We determined the effectiveness (PASI 75 or PASI < 5), and drug-survival using Kaplan-Meier estimates, and analyzed reasons for …

Impact of Early Acute Kidney Injury on Management and Outcome in Patients With Acute Respiratory Distress Syndrome: A Secondary Analysis of a Multicenter Observational Study

Contains fulltext : 208648.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To understand the impact of mild-moderate and severe acute kidney injury in patients with acute respiratory distress syndrome. DESIGN: Secondary analysis of the "Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure", an international prospective cohort study of patients with severe respiratory failure. SETTING: Four-hundred fifty-nine ICUs from 50 countries across five continents. SUBJECTS: Patients with a glomerular filtration rate greater than 60 mL/min/1.73 m prior to admission who fulfilled criteria of acute respiratory distress syndrome on day 1 and day 2 of acute …

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…

Uterus transplantation from a deceased donor

Monozygotic twinning after assisted reproductive technologies: a case report of asymmetric development and incidence during 19 years in an international group of in vitro fertilization clinics

Objective To describe a case of monozygotic twinning with asymmetric development following a single fresh embryo transfer as part of an intracytoplasmic sperm injection (ICSI) treatment. Secondarily, to report the incidence of monozygotic twinning at the IVI (Instituto Valenciano de Infertilidad) clinics. Design Case report. Setting Private fertility centers. Patient(s) A 33-year-old woman with a 2-year history of primary infertility. Intervention(s) Controlled ovarian hyperstimulation and ICSI treatment with single-embryo transfer. Main Outcome Measure(s) Incidence of monozygotic twinning at the IVI clinics. Result(s) We report a twin pregnancy after a single-embryo transfer. Twins were di…

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

Physiology and Pathology of Ovarian Hyperstimulation Syndrome

Ovarian hyperstimulation syndrome (OHSS) occurs when ovaries primed with follicle-stimulating hormone/leuteinizing hormone (LH) are subsequently exposed to human chorionic gonadotropin (hCG). The ultimate pathophysiological step underlying this clinical picture is increased vascular permeability (VP). With the administration of hCG, the expression vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) mRNA increases significantly rising to a maximum coinciding with peaked VP. Immunohistochemistry shows the presence of VEGF and VEGFR-2 proteins in the granulosa-lutein and endothelial cells of the entire corpus luteum. These findings suggest that the syndrome can be prevented…

Air bubble location inside the uterus after transfer: is the embryo really there?

Objective To demonstrate that the location of the air bubble after embryo transfer (ET) does not necessarily indicate the final embryo location. Design Case report. Setting Private clinic. Patient(s) A couple with primary infertility for whom a diagnosis of bicornuate uterus with a very open angle between horns was confirmed. Intervention(s) Laparoscopy and hysteroscopy were performed before an IVF cycle in which a single embryo was replaced. Main Outcome Measure(s) Air bubble image immediately after ET and gestational sac location 3 weeks later. Result(s) Immediately after a single ET, the air bubble was seen in the left uterine horn. Three weeks later, a gestational sac was seen in the ri…

Antral Follicle Priming Before Intracytoplasmic Sperm Injection in Previously Diagnosed Low Responders: A Randomized Controlled Trial (FOLLPRIM).

A low response to controlled ovarian hyperstimulation implies a reduced number of embryos and impaired pregnancy rate. Follicular priming with steroids before controlled ovarian hyperstimulation has been suggested to improve the subsequent ovarian response.The purpose of this study was to determine the best follicular priming protocol in low responders and to investigate the intrafollicular mechanisms triggered by steroid hormone priming.This was a single-center, randomized, parallel, open-label, controlled trial, in two phases.The setting was a university-based in vitro fertilization unit.Potential low responders (n = 99) underwent a first intracytoplasmic sperm injection cycle. Confirmed …

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…

hMG altamente purificada (hMG-HP) versus FSH + LH recombinantes en ciclos de fecundaciòn in vitro: estudio econòmico

El aumento de las parejas que necesitan tratamientos de reproduccion asistida conlleva actualmente implicaciones en los sistemas de salud, y por lo tanto la necesidad de realizar estudios de coste-beneficio. Frente al desarrollo de las gonadotropinas recombinantes, los preparados de origen urinario ofrecen costes mas economicos. En el presente estudio se comparan los resultados en terminos de coste-efectividad por gestacion evolutiva de ciclos de fecundacion in vitro en los que se empleo hMG altamente purificada (hMG-HP) frente a una combinacion de FSH y LH recombinantes. Dicho analisis se ha realizado en ciclos con agonistas y con antagonistas de la GnRH.

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…

The impact of using the combined oral contraceptive pill for cycle scheduling on gene expression related to endometrial receptivity.

STUDY QUESTION: Does the combined oral contraceptive pill (COCP) change endometrial gene expression when used for cycle programming? SUMMARY ANSWER: COCP used for scheduling purposes does not have a significant impact on endometrial gene expression related to endometrial receptivity. WHAT IS KNOWN ALREADY: Controversy exists around COCP pretreatment for IVF cycle programming as some authors claim that it might be detrimental to the live birth rate. Microarray technology applied to the study of tissue gene expression has previously revealed the behavior of genes related to endometrial receptivity under different conditions. STUDY DESIGN SIZE AND DURATION: Proof-of-concept study of 10 young h…

Determinants of endometrial receptivity.

Understanding the molecular changes that occur during the window of implantation is fundamental to our knowledge of human reproduction. Lately, the development of microarray technology has allowed this process to be studied from a global molecular perspective. In the last 2 years, researchers have focused their efforts on throwing light on the gene expression profile of the receptive endometrium. The genes hold the key to the development of the endometrium at any stage, and we have focused our work on the window of implantation. The four most recently published works in this field have revealed a long list of genes that are up- or downregulated at the time of implantation. Although these st…

P–315 Ultrasound diagnosis of adenomyosis: impact on pregnancy rate in ivf cycles with donated oocytes

Abstract Study question The aim was to evaluate in patients who underwent embryo transfer (ET) in an oocyte donation cycle, the impact of adenomyosis, diagnosed by transvaginal sonographic (TVS), on the implantation rate. Summary answer We observed a slightly higher miscarriage rate in the first trimester in patients with adenomyosis in particular in the diffuse type. What is known already What we know from literature is that there are pro studies such as Costello and Vercellini’s which show a reduced pregnancy rate and birth rate, and cons studies which find no effects at all of adenomyosis on IVF treatments. However, both show an increased risk of miscarriage and obstetric complications S…

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…

Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system.

Objective To summarize the effects of novel hormones (leptin, ghrelin, adiponectin, resistin, and PYY3-36) secreted from adipose tissue and the gastrointestinal tract that have been discovered to exert different effects on several reproductive functions, such as the hypothalamic–pituitary–gonadal axis, embryo development, implantation physiology, and clinically relevant conditions. Design A MEDLINE computer search was performed to identify relevant articles. Result(s) Leptin and ghrelin exert important roles on body weight regulation, eating behavior, and reproduction, acting on the central nervous system and target reproductive organs. As a marker of adequate nutritional stores, these horm…

A novel homologous model for noninvasive monitoring of endometriosis progression.

To date, several groups have generated homologous models of endometriosis through the implantation of endometrial tissue fluorescently labeled by green fluorescent protein (GFP) or tissue from luciferase-expressing transgenic mice into recipient animals, enabling noninvasive monitoring of lesion signal. These models present an advantage over endpoint models, but some limitations persist; use of transgenic mice is laborious and expensive, and GFP presents poor tissue penetration due to the relatively short emission wavelength. For this reason, a homologous mouse model of endometriosis that allows in vivo monitoring of generated lesions over time and mimics human lesions in recipient mice wou…

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…

Identification and Quantification of Dopamine Receptor 2 in Human Eutopic and Ectopic Endometrium: A Novel Molecular Target for Endometriosis Therapy1

Previous studies in an experimental mouse model of endometriosis have shown that the dopamine agonist (DA) cabergoline (Cb2) reduces angiogenesis and endometriotic lesions, hypothetically binding to the dopamine receptor type-2 (DRD2). To date, this has not been described in human endometrium and/or endometriotic lesions. Thus, we aimed to investigate the presence of DRD2 in said tissues. Endometrium fragments were implanted in nude mice treated with different doses of Cb2. Polymerase chain reaction assays and immunohistochemistry were performed to analyze the gene and protein expressions (respectively) of DRD2, VEGF, and VEGF receptor-2 (KDR). In addition, lesions and endometrium from wome…

Sperm survival assay for toxicity evaluation in ultrasound gels and vaginal lubricants used in reproductive medicine

Medroxyprogesterone acetate is a useful alternative to a gonadotropin-releasing hormone antagonist in oocyte donation: a randomized, controlled trial.

Objective To compare ovarian response and reproductive outcomes in oocyte donors undergoing pituitary suppression with medroxyprogesterone acetate (MPA) versus those undergoing conventional treatment with a gonadotropin-releasing hormone (GnRH) antagonist. Design A prospective, randomized, controlled trial of cycles was conducted from October 2017 to June 2019 to evaluate ovarian response in terms of the number of oocytes. The reproductive outcomes of the recipients were retrospectively analyzed later. Setting A university-affiliated private in vitro fertilization center. Patient(s) We randomly divided 318 donors into 2 groups in a 1:1 ratio. The oocytes obtained were assigned to 364 recipi…

Testing the water before swimming: satisfying the need for clinical trials of devices, media, and instruments before their use in assisted reproduction laboratories.

Ovarian stimulation does not influence the uterine immune environment in healthy infertile women.

Abstract Research question There is some controversy regarding the impact of ovarian stimulation on immune cells in women undergoing IVF. The study's aim was to determine whether ovarian stimulation affected immune uterine cells in healthy women undergoing IVF. Design This prospective cohort study included 28 patients undergoing IVF and 47 healthy oocyte donors. Endometrial biopsies were taken in a natural cycle and after ovarian stimulation. All participants had a normal karyotype, pelvic ultrasound and cervical cytology results and thyroid-stimulating hormone concentration, as well as normal glucose and insulin concentrations and inherited and acquired thrombophilia test results. Screenin…

Paracrine dialogue in implantation

We know that the implantation process requires a functionally normal embryo at the blastocyst stage and a receptive endometrium, but also a communication link between them is needed. This paracrine dialogue between 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 but not in humans. This process is a highly regulated mechanism and many molecules take part in this cross-talk. Here, we present updated information in humans on the embryonic regulation of endometrial epithelial molecules such as chemokines, adhesion and anti-adhesion molecules, and leptin dur…

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…

Dysregulated genes and their functional pathways in luteinized granulosa cells from PCOS patients after cabergoline treatment

Polycystic ovarian syndrome (PCOS) is a common reproductive disorder frequently associated with a substantial risk factor for ovarian hyperstimulation syndrome (OHSS). Dopamine receptor 2 (D2) agonists, like cabergoline (Cb2), have been used to reduce the OHSS risk. However, lutein granulosa cells (LGCs) from PCOS patients treated with Cb2 still show a deregulated dopaminergic tone (decreased D2 expression and low dopamine production) and increased vascularization compared to non-PCOS LGCs. Therefore, to understand the PCOS ovarian physiology, it is important to explore the mechanisms that underlie syndrome based on the therapeutic effects of Cb2. Here, LGCs from non-PCOS and PCOS patients …

P29.02: Assessment of placental vascularization by three-dimensional power Doppler to evaluate effect of mifepristone vs. placebo in early pregnancy

Histone deacetylase inhibition by suberoylanilide hydroxamic acid: a therapeutic approach to treat human uterine leiomyoma.

Objective To evaluate the effect of inhibition of histone deacetylases (HDACs) by suberoylanilide hydroxamic acid (SAHA) treatment of human uterine leiomyoma primary (HULP) cells in vitro on cell proliferation, cell cycle, extracellular matrix (ECM) formation, and transforming growth factor β3 (TGF-β3) signaling. Design Prospective study comparing uterine leiomyoma (UL) vs. adjacent myometrium (MM) tissue and cells with or without SAHA treatment. Setting Hospital and university laboratories. Patient(s) Women with UL without any hormone treatment. Intervention(s) Myomectomy or hysterectomy surgery in women for leiomyoma disease. Main Outcome Measure(s) HDAC activity was assessed by enzyme-li…

Bone Marrow-Derived Cells from Male Donors Do Not Contribute to the Endometrial Side Population of the Recipient

Accumulated evidence demonstrates the existence of bone marrow-derived cells origin in the endometria of women undergoing bone marrow transplantation (BMT). In these reports, cells of a bone marrow (BM) origin are able to differentiate into endometrial cells, although their contribution to endometrial regeneration is not yet clear. We have previously demonstrated the functional relevance of side population (SP) cells as the endogenous source of somatic stem cells (SSC) in the human endometrium. The present work aims to understand the presence and contribution of bone marrow-derived cells to the endometrium and the endometrial SP population of women who received BMT from male donors. Five fe…

Leptin and Leptin Receptor Are Expressed in the Human Endometrium and Endometrial Leptin Secretion Is Regulated by the Human Blastocyst1

Embryonic implantation is a crucial event for the human reproductive function. Cytokines and paracrine molecules have been proposed as putative local regulators of this process. The leptin or the OB protein has been linked to the reproductive function and inflammatory response. In the present study, we describe for the first time the expression of leptin and leptin receptor (long form) in the secretory endometrium and that endometrial leptin secretion is regulated in vitro by the human blastocyst. Leptin and leptin receptor messenger RNA and protein were identified in secretory endometrium and in cultured endometrial epithelial cells (EECs) by RT-PCR, Western blot, and immunohistochemistry.…

OP15.08: Intrauterine fetal brain damage in preeclamptic animal model: hemodynamic and histologic changes

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,…

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

Ovarian stimulation for oocyte vitrification does not modify disease-free survival and overall survival rates in patients with early breast cancer

Research question: Does ovarian stimulation for oocyte vitrification affect disease-free survival and overall survival rates in women with early breast cancer? Design: This cohort study included 259 patients with early breast cancer; 148 patients underwent ovarian stimulation, whereas 111 patients did not. Patients were treated between January 2008 and December 2016. To calculate the disease-free survival time and overall survival rate, the time of definitive surgery was defined as the starting point. The follow-up was conducted up to 5 years. Results: Exposed and non-exposed groups were comparable in tumour, node and metastases classification, Nottingham grade, hormonal receptor status, tu…

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…

Cycle scheduling for in vitro fertilization with oral contraceptive pills versus oral estradiol valerate: a randomized, controlled trial

Abstract Background Both oral contraceptive pills (OCPs) and estradiol (E2) valerate have been used to schedule gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles and, consequently, laboratory activities. However, there are no studies comparing treatment outcomes directly between these two pretreatment methods. This randomized controlled trial was aimed at finding differences in ongoing pregnancy rates between GnRH antagonist IVF cycles scheduled with OCPs or E2 valerate. Methods Between January and May 2012, one hundred consecutive patients (nonobese, regularly cycling women 18–38 years with normal day 3 hormone levels and &lt;3 previous IVF/ICSI attempts)…