Endometrial claudin-4 and leukemia inhibitory factor are associated with assisted reproduction outcome

<p>Abstract</p> <p>Background</p> <p>Claudin-4 (CLDN4) is one of several proteins that act as molecular mediators of embryo implantation. Recently, we examined immunolabeling of leukemia inhibitory factor (LIF) in the endometrial tissue of 52 IVF patients, and found that LIF staining intensity was strongly correlated with successful pregnancy initiation. In the same set of patients, we have now examined endometrial CLDN4 expression, to see how expression intensity may vary with LIF. We examined CLDN4 in the luteal phase of the menstrual cycle, immediately preceding IVF treatment. Our aim was to compare expression of LIF and CLDN4 in the luteal phase, and document these patterns as putative biomarkers for pregnancy.</p> <p>Methods</p> <p>Endometrial tissue was collected from women undergoing IVF. Endometrial biopsies were obtained during the luteal phase preceding IVF, and were then used for tissue microarray (TMA) immunolabeling of CLDN4. Previously published LIF expression data were then combined with CLDN4 expression data, to determine CLDN4/LIF expression patterns. Associations between successful pregnancy after IVF and combined CLDN4/LIF expression patterns were evaluated.</p> <p>Results</p> <p>Four patterns of immunolabeling were observed in the endometrial samples: 16% showed weak CLDN4 and strong LIF (CLDN4^-/LIF⁺); 20% showed strong CLDN4 and strong LIF (LIF⁺/CLDN4⁺); 28% showed strong CLDN4 and weak LIF (CLDN4⁺/LIF^-); and 36% showed weak CLDN4 and weak LIF (CLDN4^-/LIF^-). Successful implantation after IVF was associated with CLDN4^-/LIF⁺(p = 0.003). Patients showing this endometrial CLDN4^-/LIF⁺immunolabeling were also 6 times more likely to achieve pregnancy than patients with endometrial CLDN4⁺/LIF^-immunolabeling (p = 0.007).</p> <p>Conclusion</p> <p>The combined immunolabeling expression of CLDN4^-/LIF⁺in endometrial tissue is a potential biomarker for predicting successful pregnancy in IVF candidates.</p

Progesterone resistance in endometriosis is modulated by the altered expression of microRNA-29c and FKBP4

Context: Endometriosis results in aberrant gene expression in the eutopic endometrium (EuE) and subsequent progesterone resistance. MicroRNA (miR) microarray data in a baboon model of endometriosis showed an increased expression of miR-29c. Objectives: To explore the role of miR-29c in progesterone resistance in a subset of women with endometriosis. Design: MiR-29c expression was analyzed in the endometrium of baboons and women with or without endometriosis. The role in progesterone resistance and decidualization was analyzed by transfecting human uterine fibroblast cells with miR-29c. Patients: Subjects diagnosed with deep infiltrative endometriosis (DIE) by transvaginal ultrasound with bowel preparation underwent surgical excision of endometriosis. Eutopic secretory endometrium was collected pre- and postoperatively. Women with normal EuE and without DIE served as controls. Results: Quantitative reverse transcription polymerase chain reaction demonstrated that miR-29c expression increased, while the transcript levels of its target, FK506-binding protein 4 (FKBP4), decreased in the EuE of baboons following the induction of endometriosis. FKBP4 messenger RNA and decidual markers were statistically significantly decreased in decidualized human uterine fibroblast cells transfected with a miR-29c mimic compared with controls. Human data corroborated our baboon data and demonstrated higher expression of miR-29c in endometriosis EuE compared with normal EuE. MiR-29c was significantly decreased in endometriosis EuE postoperatively compared with preoperative tissues, and FKBP4 showed an inverse trend following radical laparoscopic resection surgery. Conclusions: We demonstrate that miR-29c expression is increased in EuE of baboons and women with endometriosis, which might contribute to a compromised progesterone response by diminishing the levels of FKBP4. Resection of DIE is likely to reverse the progesterone resistance associated with endometriosis in women

Sites of paradoxical action of the LHRH agonist (D-Trp6)-LHRH.

Immature intact and hypophysectomized female rats, which were primed with gonadotropin, were injected subcutaneously with 0.9% saline or 0.2 or 2 microgram of (D-Trp6)-LHRH once daily for 7 days. Ovarian LH/hCG receptors and ovarian weight were measured 24 hours after the last analog or saline injection. A significant reduction (P < 0.01) of ovarian LH/hCG receptors in both intact and hypophysectomized rats was observed following administration of (D-Trp6)-LHRH in doses as low as 0.2 microgram/day. A significant decrease was observed in the ovarian weight of 2 microgram-treated rats (P < 0.05). The dramatic loss of ovarian LH/hCG receptors in hypophysectomized rats induced by (D-Trp6)-LHRH may indicate that the analog has a direct effect on the ovaries

Tests for ovarian reserve: reliability and utility

Purpose of review This review discusses ovarian reserve tests for ovulation induction and their application in determining fertility capacity, and their current applications to assess risk of natural ovarian failure and to estimate ovarian function after cancer treatment. Recent findings The current arsenal of ovarian reserve tests comprises hormonal markers [basal follicle stimulating hormone, estradiol, inhibin-B, antimullerian hormone (AMH)] and ultrasonographic markers [ovarian volume, antral follicle counts (AFCs)]. These markers have limitations in terms of which test(s) should be used to reliably predict ovarian reserve with regard to accuracy, invasiveness, cost, convenience, and utility. Several studies have correlated sonographic AFCs with serum AMH levels for predicting the ovarian response to ovulation induction protocols during assisted reproduction treatments. Summary Serum AMH levels and AFC are reliable tests for predicting the ovarian response to ovulation induction. However, none of the currently employed tests of ovarian reserve can reliably predict pregnancy after assisted conception. Further, ovarian reserve tests cannot predict the onset of reproductive and hormonal menopause; thus, they should be used with caution for reproductive life-programming counseling. Moreover, there is no evidence to support the use of ovarian reserve tests to estimate the risk of ovarian sufficiency after cancer treatments

Knowledge regarding fertility preservation in cancer patients: a population-based survey among Brazilian people during the Pink October awareness event

Objective: The aim of this study was to assess the knowledge about the risk of infertility in cancer patients after treatment, and the options for fertility preservation based on a survey carried out during the 2013 Pink October campaign. Methods: This survey was carried out during the 2013 Pink October event in the most important public park of Sao Paulo, Brazil. Approximately 900 people expressed interest in learning about breast cancer prevention and fertility preservation by participating in workshops, and 242 people filled out a questionnaire. Results: Most of the respondents (78.5%) were women, and one-fourth (25%) had at least one relative with gynecological cancer. Among women over 40 years of age, 86.3% had been screened for breast cancer at some point. However, few participants (34.0%) were aware that cancer treatment can lead to infertility or had heard about fertility preservation options (22.0%). Having a relative with cancer did not influence their knowledge about fertility preservation (22.4% versus 21.3%p=0.864). However, a higher educational level was significantly associated with more knowledge about the effects of cancer on fertility and options for fertility preservation. Conclusions: The majority of participants did not have knowledge about the impact of oncologic treatment on fertility and did not know that there are options to preserve fertility in cancer patients. Awareness of infertility risk factors is an essential first step to safeguard future fertility, and therefore, more educational initiatives are needed to spread knowledge about oncofertility.Huntington Med Reprod, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP EPM, Escola Paulista Med, Dept Ginecol, Disciplina Ginecol Endocrinol, Sao Paulo, SP, BrazilUniv Sao Paulo FMUSP, Fac Med, Dept Obstet & Ginecol, Disciplina Ginecol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP EPM, Escola Paulista Med, Dept Ginecol, Disciplina Ginecol Endocrinol, Sao Paulo, SP, BrazilWeb of Scienc

The effects of bromocriptine on VEGF, kidney function and ovarian hyperstimulation syndrome in in vitro fertilization patients: a pilot study

The aim of this study was to evaluate the effects of bromocriptine on vascular endothelial growth factor (VEGF) levels in serum, kidney function and ovarian hyperstimulation syndrome in women undergoing in vitro fertilization. Twenty-eight women were randomly divided into two groups and were administered daily oral capsules for 14 days, starting on the day of human chorionic gonadotropin (hCG) administration. Group A received 2.0 mg of folic acid, whereas Group B was given 2.5 mg of bromocriptine. Physical exams, pelvic ultrasounds and laboratory evaluations were performed on the day of hCG administration and again 7 days later. No differences in ovarian hyperstimulation syndrome, urine volume, creatinine clearance, urine sodium concentration or serum VEGF levels were found between the two groups. Thus, these results indicate that bromocriptine does not affect blood levels of VEGF, kidney function or the incidence of ovarian hyperstimulation syndrome in high-risk patients subjected to in vitro fertilization.Univ São Paulo, Sch Med, Dept Obstet & Gynecol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Gynecol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Gynecol, São Paulo, BrazilWeb of Scienc