Randomized trial comparing luteinizing hormone supplementation timing strategies in older women undergoing ovarian stimulation

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An evaluation of the use and handling errors of currently available recombinant human follicle-stimulating hormone pen injectors by women with infertility and fertility nurses

Background: This study compared preference ratings of women with infertility and nurses before and after simulated injection, and handling errors, with the GONAL-f®, Bemfola®, Ovaleap® and Rekovelle® pen injectors. Research design and methods: Injector-naïve women and injector-experienced fertility nurses tested injectors with masked labels in a randomized testing order. Injections were made into a foam pad and injectors were rated before and after use. Handling errors were recorded during the study. Ratings and errors were compared between pen injectors using ordinal or Poisson linear mixed models adjusted for testing order. Results: 120 women and 60 nurses participated. All participants tested GONAL-f and Bemfola injectors. Because of their similarity, participants tested either Rekovelle (71 women; 30 nurses) or Ovaleap (49 women; 30 nurses) injectors. The ratings from women were higher for GONAL-f vs other injectors after simulated use (p < 0.001 for all comparisons). Fertility nurses rated GONAL-f injector higher than other injectors both before and after use (p < 0.01 for all comparisons). Adjusted rates of total handling errors were lower with the GONAL-f vs other injectors (p < 0.001 for all comparisons) for both groups. Conclusions: GONAL-f injector was rated significantly higher than other injectors, which may be related to less handling errors observed with the GONAL-f injector. ispartof: EXPERT OPINION ON DRUG DELIVERY vol:16 issue:9 pages:1003-1014 ispartof: location:England status: publishe

Decision points for individualized hormonal stimulation with recombinant gonadotropins for treatment of women with infertility

It is essential that fertility treatment is individualized based on a thorough diagnostic work-up, with treatment tailored to the patients' requirements. This individualization should be kept in mind during the main decision points that occur before and during treatment. Treatment customization must include consideration of both the woman and her partner involved in the process together, including their collective treatment goals. Once treatment goals have been agreed and diagnostic evaluations performed, personalization based on patient characteristics, together with an understanding of treatment goals and patient preferences, enables the selection of appropriate treatments, protocols, products and their dosing. Following treatment initiation, monitoring and adaptation of product and dose can then ensure optimal outcomes. Currently, it is not possible to base treatment decisions on every characteristic of the patient and personalization is based on biomarkers that have been identified as the most relevant. However, in the future, the use of artificial intelligence coupled with continuous monitoring should enable greater individualization and improve outcomes. This review considers the current state-of-the-art related to decision points during individualized treatment of female infertility, before looking at future developments that might further assist in making individualized treatment decisions, including the use of computer-assisted decision making. ispartof: GYNECOLOGICAL ENDOCRINOLOGY vol:35 issue:12 pages:1027-1036 ispartof: location:England status: publishe

Immunobiology of pregnancy: from basic science to translational medicine

: Embryo implantation failure and spontaneous abortions represent the main causes of infertility in developed countries. Unfortunately, incomplete knowledge of the multiple factors involved in implantation and fetal development keeps the success rate of medically assisted procreation techniques relatively low. According to recent literature, cellular and molecular mechanisms of 'immunogenic tolerance' towards the embryo are crucial to establish an 'anti-inflammatory' state permissive of a healthy pregnancy. In this review we dissect the role played by the immune system in the endometrial-embryo crosstalk, with a particular emphasis towards the fork-head-box-p3 (Foxp3+) CD4+CD25+ regulatory T (Treg) cells and discuss the most recent therapeutic advances in the context of early immune-mediated pregnancy loss

Dosing Characteristics of Recombinant Human Luteinizing Hormone or Human Menopausal Gonadotrophin-Derived LH Activity in Patients Undergoing Ovarian Stimulation: A German Fertility Database Study

Objectives: The aim of the study was to evaluate dosing of recombinant human luteinizing hormone (r-hLH) or human menopausal gonadotrophin (hMG)-derived medications with LH activity in ovarian stimulation (OS) cycles for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Design: A non-interventional study was performed to analyse data from the German RecDate database (January 2007-December 2011). Participants/Materials, Setting, Methods: Starting/total r-hLH/hMG dose, OS duration/cycle number, r-hLH/hMG initiation day (first day of administration), and population/cycle characteristics were assessed in women (&amp; GE;18 years) undergoing OS for IVF/ICSI using r-hLH or hMG-derived medications (excluding corifollitropin alfa, clomiphene citrate, letrozole, mini/micro-dose human chorionic gonadotrophin, and urofollitropin alone). Data were summarized descriptively. Results: 67,858 identified cycles utilized medications containing r-hLH (10,749), hMG (56,432), or both (677). Mean (standard deviation) OS duration with r-hLH and hMG was 10.1 (4.43) and 9.8 (6.16) days, respectively. Median (25th-75th percentile) r-hLH starting dose (75.0 [75.0-150.0] IU) was consistent across patients regardless of age, infertility diagnosis, or gonadotrophin-releasing hormone (GnRH) protocol. Median (25th-75th percentile) hMG-derived LH activity starting dose was 225.0 (150.0-300.0) IU, regardless of GnRH protocol, but was lower in women aged &lt;35 years and those with ovulation disorders/polycystic ovary syndrome. Median (25th-75th percentile) total dose for r-hLH (750.0 [337.5-1,125.0] IU) and hMG-derived LH activity (1,575.0 [750.0-2,625.0] IU) varied according to patients' age, infertility diagnosis, cycle number, and r-hLH/hMG initiation day. GnRH antagonist use resulted in a numerically higher median total hMG-derived LH activity dose than GnRH agonist use. Limitations: The data used in this study were taken from electronic medical records relating to a specific timeframe (2007-2011) and therefore may not accurately reflect current clinical practice; however, it is likely that the differences between the two compounds would be maintained. Additionally, secondary data sources may suffer from uniformity and quality issues. Conclusions: The standard of care for OS cycles is described with respect to IVF/ICSI treatment including an LH component in Germany during the specified timeframe

Biosimilar recombinant follitropin alfa preparations versus the reference product (Gonal-F®) in couples undergoing assisted reproductive technology treatment : a systematic review and meta-analysis

Acknowledgments Authors would like to thank Dr. Rui Wang (Department of Obstetrics and Gynecology, University of Monash) who contributed to the statistical analysis. Medical writing assistance was provided by Evelina Matekonyte, inScience Communications, Springer Healthcare Ltd., London, UK, and funded by Merck KGaA, Darmstadt, Germany. Funding This study was funded by Merck KGaA, Darmstadt, Germany. Merck KGaA (Darmstadt, Germany) designed and approved the study, took part in data collection and data analysis, and contributed to the data interpretation and final draft of the manuscript. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.Peer reviewedPublisher PD

Prep1 Controls Insulin Glucoregulatory Function in Liver by Transcriptional Targeting of SHP1 Tyrosine Phosphatase

AbstractObjective. We have investigated the function of the Prep1 gene in insulin-dependent glucose homeostasis in liver. Research design and methods. Prep1 action on insulin glucoregulatory function has been analyzed in liver of Prep1-hypomorphic mice (Prep1(i/i)), which express 2 to 3% of Prep1 mRNA. Results. Based on euglycemic hyperinsulinemic clamp studies, pyruvate tolerance tests and measurement of glycogen content, livers from Prep1(i/i) mice feature increased sensitivity to insulin. Tyrosine phosphorylation of both insulin receptor (IR) and IRS1/2 was significantly enhanced in Prep1(i/i) livers accompanied by a specific down-regulation of the SYP and SHP1 tyrosine phosphatases. Prep1 overexpression in HepG2 liver cells upregulated SYP and SHP1 and inhibited insulin-induced IR and IRS1/2 phosphorylation and was accompanied by reduced glycogen content. Consistently, overexpression of the Prep1 partner Pbx1 but not of p160MBP, mimicked Prep1 effects on tyrosine phosphorylations, glycogen content and on SYP and SHP1 expression. In Prep1 overexpressing cells, antisense silencing of SHP1, but not that of SYP, rescued insulin-dependent IR phosphorylation and glycogen accumulation. Both Prep1 and Pbx1 bind SHP1 promoter at a site located between nt -2113 and -1778. This fragment features enhancer activity and induces luciferase function by 7, 6 and 30-fold, respectively, in response to Prep1, Pbx1 or both. Conclusions. SHP1, a known silencer of insulin signal, is a transcriptional target of Prep1. In liver, transcriptional activation of SHP1 gene by Prep1 attenuates insulin signal transduction and reduces glucose storage

The Microalga Skeletonema marinoi Induces Apoptosis and DNA Damage in K562 Cell Line by Modulating NADPH Oxidase

Chronic myeloid leukemia (CML) is a myeloproliferative disease that activates multiple signaling pathways, causing cells to produce higher levels of reactive oxygen species (ROS). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are a major generator of ROS in leukemia, and marine natural products have shown promising activities for the treatment of hematopoietic malignancies. In the present study, we investigated the effect of the marine microalga Skeletonema marinoi (S.M.), a ubiquitous diatom that forms massive blooms in the oceans, on the human leukemia cell line K562. The effects of S.M. extract on cell viability, production of ROS, nitric oxide (NO), and apoptosis were examined. In this preliminary work, S.M. was able to decrease cell viability (p < 0.05) and increase apoptosis levels (p < 0.05) in K562 cells after 48 h of treatment. In addition, the levels of NOX, NO, and malondialdehyde (MDA) were reduced in K562-treated cells (p < 0.05), whereas the levels of SOD, CAT, and GPx increased during treatment (p < 0.05). Finally, analyzing Bax and Bcl-2 expression, we found a significant increase in the proapoptotic protein Bax and a sustained decrease in the antiapoptotic protein Bcl-2 (p < 0.05) in the K562-treated cells