Publications by authors named "Roxana M Popovici"

8 Publications

  • Page 1 of 1

Endometrial Dating Method Detects Individual Maturation Sequences During the Secretory Phase.

In Vivo 2020 Jul-Aug;34(4):1951-1963

Fertility-Center Munich, Munich, Germany.

Background/aim: This study assessed whether a new immunohistochemical dating method allows precise endometrial dating allowing optimal timing for embryo transfer.

Patients And Methods: A novel method was used for endometrial dating, with parameters including menstrual cycle days, Noyes histological criteria, along with immunohistochemical expression pattern of estrogen and progesterone receptors and proliferation marker Ki-67. Endometrial maturation was analyzed on days +5 to +10 after ovulation or progesterone administration in 217 biopsies from 151 subfertile patients during the secretory phase.

Results: Endometrial maturation varied individually, occurring 1.68±1.67 days late. Comparison of histological maturation with clinical days after ovulation showed a delay of about 2 days.

Conclusion: Endometrial maturation requires 8 days, rather than the expected 6 days, to reach the histological mid-secretory phase. This is not a delay and is also seen in fertile patients. The new analysis method used is superior to that using Noyes criteria alone and provides a better basis for determining conditions for optimal timing of embryo transfers.
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http://dx.doi.org/10.21873/invivo.11992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439867PMC
April 2020

Psychotherapy With Somatosensory Stimulation for Endometriosis-Associated Pain: The Role of the Anterior Hippocampus.

Biol Psychiatry 2018 11 16;84(10):734-742. Epub 2017 Jan 16.

Institute of Medical Psychology, Ludwig-Maximilians-Universität München, Munich; Division Integrative Health Promotion, University of Applied Sciences, Coburg, Germany.

Background: Endometriosis is a gynecological disorder affecting 6%-10% of all women in their reproductive age. There is an emerging view in the literature that psychological trauma plays a central role in the pathogenesis of pelvic pain, one of the core symptoms of endometriosis. Here we report central nervous system mechanisms of a novel combination of psychotherapy and somatosensory stimulation that has recently shown remarkable effects in reducing pain, anxiety, and depressive symptoms in these patients.

Methods: We conducted a randomized controlled trial; 67 patients with severe endometriosis-associated pain (maximum pain: 7.6 ± 2.0, average pain: 4.5 ± 2.0 on a 10-point numeric rating scale) were included in the study and randomly allocated to intervention (35 patients) or waitlist control (32 patients) groups. Resting-state functional magnetic resonance imaging was used to assess brain connectivity of these patients at baseline, after 3 months of therapy, and after 6 months. The analysis focused on the hippocampus.

Results: We identified a cortical network comprising the right anterolateral hippocampus-a region modulating the hypothalamic-pituitary-adrenal axis-and somatosensory, viscerosensory, and interoceptive brain regions. Regression analysis showed that reduction in connectivity predicted therapy-induced improvement in patients׳ anxiety.

Conclusions: We have identified a putative neurobiological mechanism underlying the potent combination of psychotherapy and somatic stimulation in treating symptoms of endometriosis.
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http://dx.doi.org/10.1016/j.biopsych.2017.01.006DOI Listing
November 2018

Psychotherapy With Somatosensory Stimulation for Endometriosis-Associated Pain: A Randomized Controlled Trial.

Obstet Gynecol 2016 11;128(5):1134-1142

Institute of Medical Psychology, Ludwig-Maximilians-Universität München, and the Departments of Neuroradiology and Obstetrics and Gynecology and the Clinic for Neurology, Technische Universität München, Munich, Practice for Psychotherapeutic Medicine, Diessen, the Department of Gynecologic Endocrinology and Fertility Disorders, Heidelberg University Women's Hospital, Heidelberg, and Somatosensory and Autonomic Therapy Research, Institute for Neuroradiology, Hannover Medical School, Hannover, Germany.

Objective: To evaluate whether psychotherapy with somatosensory stimulation is effective for the treatment of pain and quality of life in patients with endometriosis-related pain.

Methods: Patients with a history of endometriosis and chronic pelvic pain were randomized to either psychotherapy with somatosensory stimulation (ie, different techniques of acupuncture point stimulation) or wait-list control for 3 months, after which all patients were treated. The primary outcome was brain connectivity assessed by functional magnetic resonance imaging. Prespecified secondary outcomes included pain on 11-point numeric rating scales (maximal and average global pain, pelvic pain, dyschezia, and dyspareunia) and physical and mental quality of life. A sample size of 30 per group was planned to compare outcomes in the treatment group and the wait-list control group.

Results: From March 2010 through March 2012, 67 women (mean age 35.6 years) were randomly allocated to intervention (n=35) or wait-list control (n=32). In comparison with wait-list controls, treated patients showed improvements after 3 months in maximal global pain (mean group difference -2.1, 95% confidence interval [CI] -3.4 to -0.8; P=.002), average global pain (-2.5, 95% CI -3.5 to -1.4; P<.001), pelvic pain (-1.4, 95% CI -2.7 to -0.1; P=.036), dyschezia (-3.5, 95% CI -5.8 to -1.3; P=.003), physical quality of life (3.8, 95% CI 0.5-7.1, P=.026), and mental quality of life (5.9, 95% CI 0.6-11.3; P=.031); dyspareunia improved nonsignificantly (-1.8, 95% CI -4.4 to 0.7; P=.150). Improvements in the intervention group remained stable at 6 and 24 months, and control patients showed comparable symptom relief after delayed intervention.

Conclusion: Psychotherapy with somatosensory stimulation reduced global pain, pelvic pain, and dyschezia and improved quality of life in patients with endometriosis. After 6 and 24 months, when all patients were treated, both groups showed stable improvements.

Clinical Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01321840.
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http://dx.doi.org/10.1097/AOG.0000000000001691DOI Listing
November 2016

Improving fertility preservation in cancer: ovarian tissue cryobanking followed by ovarian stimulation can be efficiently combined.

Fertil Steril 2011 Jan 24;95(1):342-4. Epub 2010 Aug 24.

Institute Fiore, Cantonal Hospital, St. Gallen, Switzerland.

This pilot study evaluated whether combination of partial removal of ovarian tissue for cryobanking followed by ovarian stimulation and cryopreservation of oocytes can improve the efficacy of fertility preservation without further delaying cancer treatment. Initial partial removal of ovarian tissue did not substantially affect the average number and quality of retrieved oocytes after ovarian stimulation in this study.
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http://dx.doi.org/10.1016/j.fertnstert.2010.07.1074DOI Listing
January 2011

Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase.

Fertil Steril 2009 Oct 18;92(4):1360-1365. Epub 2008 Oct 18.

Department of Gynecologic Endocrinology and Reproductive Medicine, Women's University Hospital, University of Heidelberg, Heidelberg, Germany.

Objective: To analyze if oocytes can be obtained in all patients before cancer treatment within 2 weeks by initiating ovarian stimulation during the follicular or luteal phase.

Design: Prospective controlled multicenter trial.

Setting: Four university-based centers.

Patient(s): Forty cancer patients before chemotherapy.

Intervention(s): Twenty-eight patients were stimulated with gonadotropins in the follicular phase (group I). In 12 patients (group II), ovarian stimulation was initiated in the luteal phase, and these received GnRH antagonists and recombinant FSH. In 14 patients, 143 oocytes were further processed for fertilization by intracytoplasmic sperm injection (ICSI).

Main Outcome Measure(s): Number of oocytes aspirated after ovarian stimulation, cumulative FSH/hMG dosage, viability and maturity of oocytes, and fertilization rate by ICSI.

Result(s): Patients in group I (age 27.6 +/- 4.9 yrs) were stimulated on average for 10.6 days, and patients in group II (age 31.2 +/- 5.7 yrs) for 11.4 days. Total amount of FSH was on average 2,255 IU (I) and 2,720 IU (II) per patient. Average and median numbers of aspirated oocytes were, respectively, 13.1 and 11.5 (I) versus 10.0 and 8.5 (II); 83.7% (I) and 80.4% (II) of the oocytes were mature and viable and could be treated by ICSI. Fertilization rate was 61.0% (I) versus 75.6% (II).

Conclusion(s): This pilot study suggests that oocytes can be obtained before cancer treatment efficiently irrespective of the phase of the menstrual cycle.
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http://dx.doi.org/10.1016/j.fertnstert.2008.08.011DOI Listing
October 2009

The long pentraxin PTX3 in human endometrium: regulation by steroids and trophoblast products.

Endocrinology 2008 Mar 29;149(3):1136-43. Epub 2007 Nov 29.

Department of Gynecological Endocrinology and Reproductive Medicine, University of Heidelberg, Voss Strasse 9, 69115 Heidelberg, Germany.

Human implantation is characterized by blastocyst attachment to endometrial epithelial cells followed by invasion of trophoblast into the maternal decidua. There has been an increasing amount of data linking higher levels of the pentraxin PTX3, a long pentraxin, to embryo implantation. PTX3 levels were found to be higher in patients with preeclampsia and intrauterine growth restriction, both conditions caused by faulty implantation. Furthermore, PTX3 knockout mice have reduced fertility due to cumulus oopherus malformation as well as implantation failure. In a human implantation model, we and others have shown that trophoblast action on endometrial stromal cells induces PTX3 expression. In this study, we analyzed PTX3 expression throughout the menstrual cycle as well as its regulation by hormones involved in the implantation process. We also compared PTX3 expression in stromal cells induced by trophoblast conditioned medium to its induction by trophoblast coculture. PTX3 mRNA expression in human endometrial stromal cells is regulated by progesterone, estrogen, and IL-1 but not human chorionic gonadotropin and is increased by both trophoblast-conditioned medium as well as trophoblast explants. PTX3 protein production and regulation by these factors is shown by Western blot. Based on these findings, we conclude that estradiol and progesterone are involved in PTX3 induction and regulation during implantation. Also, of the factors secreted by trophoblast, IL-1beta induces PTX3 in human endometrial stromal cells.
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http://dx.doi.org/10.1210/en.2007-1302DOI Listing
March 2008

Gene expression profiling of human endometrial-trophoblast interaction in a coculture model.

Endocrinology 2006 Dec 31;147(12):5662-75. Epub 2006 Aug 31.

Department of Gynecological Endocrinology and Reproductive Medicine, University of Heidelberg, Voss Strasse 9, 69115 Heidelberg, Germany.

Investigating the interaction of human endometrium and trophoblast during implantation is difficult in vitro and impossible in vivo. This study was designed to analyze the effect of trophoblast on endometrial stromal cells during implantation by comprehensive gene profiling. An in vitro coculture system of endometrial stromal cells with first-trimester trophoblast explants was established. Trophoblast and endometrial stromal cells were separated after 24 h. Gene expression of endometrial stromal cells after coculture was compared with the gene expression of endometrial stromal cells cultured alone by microarray analysis. We confirmed the expression of distinct genes using real-time PCR. Genes up-regulated included those for inflammatory response, immune response, and chemotaxis (pentraxin-related gene 3, chemokine ligands, IL-8, IL-1 receptors, IL-18 receptor, IL-15, IL-15 receptor, TNF-alpha-induced protein 6, and IL-6 signal transducer), regulators of cell growth (IGF-binding proteins 1 and 2) and signal transduction. Also up-regulated were genes for growth and development, glucose metabolism, and lipid metabolism: DKK-1, WISP, IGF-II, hydroxysteroid 11beta-dehydrogenase 1, hydroxyprostaglandin dehydrogenase 15, prostaglandin E synthase, prostaglandin F receptor, aldehyde dehydrogenase 1 family, member A3 and phosphatidic acid phosphatase type 2B. Other genes included genes for cell-cell signaling (pre-B-cell colony-enhancing factor 1), proteolysis, calcium ion binding, regulation of transcription, and others. Down-regulated genes included genes for proteolysis (MMP-11 and mitochondrial intermediate peptidase), genes for cell death (caspase 6, death-associated protein kinase 1, and histone deacetylase 5), transcription factors (sex determining region Y-box 4, dachshund homolog 1, ets variant gene 1, and zinc finger protein 84 and 435), and genes for humoral immune response (CD24 antigen). Trophoblast has a significant impact on endometrial stromal cell gene expression. Some of the genes regulated by trophoblast in endometrial stromal cells are already known to be regulated by progesterone and show the endocrine function of trophoblast during pregnancy. Others are genes so far unknown to play a role in endometrial-trophoblast interaction and open a wide field of investigation.
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http://dx.doi.org/10.1210/en.2006-0916DOI Listing
December 2006

Galectin-9: a new endometrial epithelial marker for the mid- and late-secretory and decidual phases in humans.

J Clin Endocrinol Metab 2005 Nov 16;90(11):6170-6. Epub 2005 Aug 16.

Department of Gynecological Endocrinology and Reproductive Medicine, University of Heidelberg, Voss Strasse 9, 69115 Heidelberg, Germany.

Context: The galectin family has been reported to play a role in the regulation of cell growth, cell adhesion, apoptosis, inflammation, and immunomodulation, all of which are important for endometrial function, as well as implantation.

Objective: The objective of the study was to investigate the expression and regulation of galectin-9, a beta-galactoside-binding lectin in the human endometrium.

Design: Galectin-9 mRNA and protein were analyzed in dated endometrial biopsies throughout the menstrual cycle and in human early-pregnancy decidua, as well as in the different endometrial cell compartments. Regulation of galectin-9 by estradiol, progesterone, epidermal growth factor, and interferon-gamma in endometrial epithelial cells in vitro was studied.

Results: Galectin-9 mRNA analyzed by RNase protection assay is expressed in the human endometrium, specifically in the human endometrial epithelial cells but not in stromal or immune cells. It is expressed at very low concentrations during the proliferative phase and the early-secretory phase and shows a sharp and significant increase in the mid- and late-secretory phases, the window of implantation, as well as in the decidua. Accordingly, galectin-9 protein is also exclusively increased in human endometrial epithelial cells during the mid- and late-secretory phases and in the decidua, however, not in endometrial stromal cells or decidualized cells in vivo or in vitro. A regulation in vitro by estradiol, progesterone, epidermal growth factor, and interferon-gamma could not be detected.

Conclusions: Based on these findings and on the functional studies of other galectins, we suggest galectin-9 as a novel endometrial marker for the mid- and late-secretory and decidual phases.
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http://dx.doi.org/10.1210/jc.2004-2529DOI Listing
November 2005