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…

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

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…

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…

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…

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…

Effect of Antiangeogenic Treatment on Peritoneal Endometriosis-Associated Nerve Fibers

P–446 Controlled ovarian stimulation protocols for oocyte vitrification induce differential gene expression profiles in primary tumours of breast cancer

Abstract Study question Could controlled ovarian stimulation (COS) protocols used in fertility preservation (FP) impact on malignant cell proliferation and tumour molecular profiling of breast cancer (BC) patients? Summary answer Letrozole supplementation during ovarian stimulation for oocyte vitrification could be considered as a safe procedure in estrogen-dependent BC patients undergoing FP. What is known already High estradiol levels associated to COS could promote changes in gene expression in estrogen-positive BC tumors. Estradiol levels reached during the ovarian stimulation could aggressively promote malignant cell proliferation and cell migration to adjacent organs. Aromatase inhibi…

[Fertility preservation in the oncology patient].

In recent years, medical advances have substantially improved survival of cancer patients, generating growing concern about the quality of life of the survivors. Increased attention has been paid to reproductive problems after oncological treatments. International guidelines on fertility preservation in cancer patients require that healthcare teams discuss, as early as possible, the impact of cancer treatments on fertility and encourage access to fertility preservation techniques. The development of these techniques in women is a recent effort and many patients and health care providers are not familiar with their rapid expansion. This article discusses indications, results, and risks of th…

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…

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, …

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 …

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…

Occurrence of Edwardsiella tarda in wild European eels Anguilla anguilla from Mediterranean Spain

Pure cultures of Edwarsiella tarda were isolated from body ulcers and internal organs of wild European eels caught in a Mediterranean freshwater coastal lagoon (Albufera Lake, Valencia, Spain) over a 1 yr period. Overall, the E. tarda isolation rate from wild eels was 9%, but this increased to 22.8% in diseased individuals. All 22 E. tarda isolates belonged to the 'wild-type' biogroup of the species and were virulent for eels (lethal dose that kills 50% of exposed individuals [LD50 dose]: 10(4.85) to 10(6.83) CFU ind.(-1)), and therefore represented the aetiological agent of the haemorrhagic disease observed in wild European eels. The E. tarda isolates and E. tarda CECT 894T type strain wer…

First description of nonmotileVibrio vulnificusstrains virulent for eels

Nonmotile Vibrio vulnificus strains were isolated as pure cultures from body ulcers and internal organs of wild diseased European eels caught in a Mediterranean freshwater coastal lagoon. All 54 V. vulnificus isolates were nonmotile, indole-, ornithine decarboxilase-, mannitol- and cellobiose-positive, developed the opaque variant in culture, belonged to the O-antigenic serovar A and were highly virulent for eels by both intraperitoneal injection and immersion challenges. The nonmotile phenotype found in our V. vulnificus isolates was stable: nonmotile cells were always recovered from experimentally infected eels; no variation in the immobility of the V. vulnificus cells was observed for re…

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/…

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…

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

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 …

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…

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 …

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…

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