The risk of ectopic pregnancy following GnRH agonist triggering compared with hCG triggering in GnRH antagonist IVF cycles.

PurposeThe aim of this study was to compare the incidence of ectopic pregnancy in GnRH agonist triggered IVF cycles with intensive luteal support versus hCG triggered IVF cycles.MethodsThis study was conducted as a retrospective cohort analysis of women who underwent IVF treatment employing GnRH agonist or recombinant hCG (rhCG) triggers during 2-year period. The medical charts of women who achieved pregnancies were reviewed and their demographic characteristics, infertility reasons and IVF data were recorded. A multiple logistic regression analysis was performed to estimate the association between the triggering medication used to stimulate final oocyte maturation (GnRHa or rhCG) and EP, with adjustment for important confounders: the day of embryo transfer (ETD), the etiology of infertility and estrogen level at the time of triggering.ResultsThe number of metaphase II oocytes, fertilized oocytes and good quality embryos were significantly higher in the GnRH agonist triggered group compared with the hCG triggered group (p < 0.001 for all). The clinical pregnancy and implantation rates in the hCG triggered cycles were 38.6 and 31.1 %, respectively and 24.7 and 22 %, respectively in the triptorelin triggered cycles. The ectopic pregnancy rates were 5.3 % in the triptorelin triggered group and 1.4 % in the hCG triggered group. The trigger medication and the day of embryo transfer were found to have a significant effect on the probability of developing ectopic pregnancy (p = 0.028, p = 0.046 respectively). However, the estrogen level was not found to have a significant effect on the probability of developing ectopic pregnancy (p = 0.447).ConclusionsThe reasons for higher ectopic pregnancy rates in GnRH agonist triggered cycles relative to hCG triggered cycles may be the decreased receptivity of the endometrium due to insufficient luteal support and higher implantation potential of embryos in correlation with a higher number of good quality embryos obtained in these cycles

Letrozole versus human menopausal gonadotrophin in women undergoing intrauterine insemination

This pilot study was conducted to compare the results of intrauterine insemination (IUI) under ovarian stimulation with either letrozole (Femara) or human menopausal gonadotrophin (HMG). A randomized controlled trial was conducted. Eighty women aged 20-35 years with unexplained infertility of at least 2 years' duration were randomized according to a computer-generated randomization list into the letrozole group and the HMG group. Letrozole was administered at 5 mg/day from day 3 to day 7 of the IUI cycle. HMG injections were started on day 3 at a dose of 75 IU for women under 30 years old and 150 IU for women over 30 years old and monitored periodically by vaginal ultrasound and oestradiol concentrations. The variables selected for analysis were clinical pregnancy rate, endometrial thickness, length of follicular phase and number of preovulatory follicles. No statistically significant difference in clinical pregnancy rates per cycle was found for patients in the letrozole or HMG group (18.4 versus 15.7%). Cost was significantly higher in the HMG stimulation cases (P < 0.001) and no injections were required in the letrozole group. In conclusion, letrozole offers a new treatment regimen in ovarian stimulation regimens for IUI that is cost effective, simple and convenient for the patients

The risk of ectopic pregnancy following GnRH agonist triggering compared with hCG triggering in GnRH antagonist IVF cycles.

PurposeThe aim of this study was to compare the incidence of ectopic pregnancy in GnRH agonist triggered IVF cycles with intensive luteal support versus hCG triggered IVF cycles.MethodsThis study was conducted as a retrospective cohort analysis of women who underwent IVF treatment employing GnRH agonist or recombinant hCG (rhCG) triggers during 2-year period. The medical charts of women who achieved pregnancies were reviewed and their demographic characteristics, infertility reasons and IVF data were recorded. A multiple logistic regression analysis was performed to estimate the association between the triggering medication used to stimulate final oocyte maturation (GnRHa or rhCG) and EP, with adjustment for important confounders: the day of embryo transfer (ETD), the etiology of infertility and estrogen level at the time of triggering.ResultsThe number of metaphase II oocytes, fertilized oocytes and good quality embryos were significantly higher in the GnRH agonist triggered group compared with the hCG triggered group (p &lt; 0.001 for all). The clinical pregnancy and implantation rates in the hCG triggered cycles were 38.6 and 31.1 %, respectively and 24.7 and 22 %, respectively in the triptorelin triggered cycles. The ectopic pregnancy rates were 5.3 % in the triptorelin triggered group and 1.4 % in the hCG triggered group. The trigger medication and the day of embryo transfer were found to have a significant effect on the probability of developing ectopic pregnancy (p = 0.028, p = 0.046 respectively). However, the estrogen level was not found to have a significant effect on the probability of developing ectopic pregnancy (p = 0.447).ConclusionsThe reasons for higher ectopic pregnancy rates in GnRH agonist triggered cycles relative to hCG triggered cycles may be the decreased receptivity of the endometrium due to insufficient luteal support and higher implantation potential of embryos in correlation with a higher number of good quality embryos obtained in these cycles

EDA2R-NIK signalling promotes muscle atrophy linked to cancer cachexia.

Skeletal muscle atrophy is a hallmark of the cachexia syndrome that is associated with poor survival and reduced quality of life in patients with cancer. Muscle atrophy involves excessive protein catabolism and loss of muscle mass and strength. An effective therapy against muscle wasting is currently lacking because mechanisms driving the atrophy process remain incompletely understood. Our gene expression analysis in muscle tissues indicated upregulation of ectodysplasin A2 receptor (EDA2R) in tumour-bearing mice and patients with cachectic cancer. Here we show that activation of EDA2R signalling promotes skeletal muscle atrophy. Stimulation of primary myotubes with the EDA2R ligand EDA-A2 triggered pronounced cellular atrophy by induction of the expression of muscle atrophy-related genes Atrogin1 and MuRF1. EDA-A2-driven myotube atrophy involved activation of the non-canonical NFĸB pathway and was dependent on NFκB-inducing kinase (NIK) activity. Whereas EDA-A2 overexpression promoted muscle wasting in mice, deletion of either EDA2R or muscle NIK protected tumour-bearing mice from loss of muscle mass and function. Tumour-induced oncostatin M (OSM) upregulated muscle EDA2R expression, and muscle-specific oncostatin M receptor (OSMR)-knockout mice were resistant to tumour-induced muscle wasting. Our results demonstrate that EDA2R-NIK signalling mediates cancer-associated muscle atrophy in an OSM-OSMR-dependent manner. Thus, therapeutic targeting of these pathways may be beneficial in prevention of muscle loss