Initial hCG Levels in Ectopic Pregnancies After Embryo Transfer: Use of the Bayes Classifier for Risk Assessment.

OBJECTIVE: To determine whether the Bayes classifier can be used to distinguish between an ectopic and intrauterine pregnancy following embryo transfer based on early human chorionic gonadotropin (hCG) levels. STUDY DESIGN: Retrospective chart review of patients undergoing in vitro fertilization and diagnosed with a singleton intrauterine or with an ectopic pregnancy. Blood was drawn for hCG levels between days 12 and 20 after transvaginal oocyte aspiration. Statistical analysis was performed using a mixed effects model and the Bayes classifier. RESULTS: Singleton intrauterine (n=91) and ectopic gestations (n=14) were analyzed. hCG levels increased by 51% daily in both groups, but levels in ectopic pregnancies were only 14% of those from the control group on the same day (p<1×10-15). Using the Bayes classifier, an hCG value <18 IU/L indicated a large probability (>75%) that the pregnancy was ectopic. There was no statistically significant difference in regards to endometrial thickness (p=0.77), fresh or frozen embryo transfer (p=0.53), number of embryos transferred (p=0.13), donor or autologous oocytes (p=0.76), or the day of hCG draw (p=0.13 and 0.43 for first and second measurement). CONCLUSION: The Bayes classifier can be used as a tool to alert the healthcare provider of a possible ectopic gestation.

Live Birth from Electively Cryopreserved Oocytes: A Feasible Option for Couples Opposed to Embryo Cryopreservation A Case Report.

BACKGROUND: This case report describes a relatively novel indication for oocyte cryopreservation. CASE: A couple undergoing infertility treatment at our institution was opposed to embryo cryopreservation for religious reasons. After multiple unsuccessful infer- tility treatment cycles in- cluding ovulation induction combined with' artificial insemination as well as cycles of therapy with in vitro maturation, we were able to offer them fertilization of a limited number of oocytes followed by oocyte cryopreservation. Since our initial fresh embryo transfer was unsuccessful, the thawing of a limited number of these oocytes prevented a second oocyte retrieval. The couple had 3 oocytes thawed and fertilized and had a successful term birth. CONCLUSION: Elective oocyte cryopreservation is a feasible option for successful pregnancy in patients opposed to embryo cryopreservation.

Hormonal and nonhormonal treatment of vasomotor symptoms.

This article focuses on the cause, pathophysiology, differential diagnosis of, and treatment options for vasomotor symptoms. In addition, it summarizes important points for health care providers caring for perimenopausal and postmenopausal women with regard to health maintenance, osteoporosis, cardiovascular disease, and vaginal atrophy. Treatment options for hot flashes with variable effectiveness include systemic hormone therapy (estrogen/progestogen), nonhormonal pharmacologic therapies (selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, clonidine, gabapentin), and nonpharmacologic therapy options (behavioral changes, acupuncture). Risks and benefits as well as contraindications for hormone therapy are further discussed.

Successful increase in uterine volume and subsequent pregnancy in a patient with a history of radiation and chemotherapy.

A 26-year-old woman with a history of cranial radiation and chemotherapy desired pregnancy. Pelvic ultrasound scanning demonstrated a small uterine volume of 7 mL. After 25 weeks of estrogen therapy, her uterine volume increased to 37 mL. The patient had an uncomplicated pregnancy with the use of donor oocytes and delivered a term healthy daughter.

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

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.

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

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.

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

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.