A prospective, single-centre, single-arm, open label study of the long term use of a gonadotropin releasing hormone agonist (Triptorelin SR, 11.25 mg) in combination with Tibolone add-back therapy in the management of chronic cyclical pelvic pain.

BACKGROUND: Chronic cyclic pelvic pain (CCPP) affects women's quality of life and pituitary downregulation is often used for symptomatic relief. However, prolonged suppression of ovarian function is associated with menopausal side effects and can lead to osteoporosis. Currently, the use of gonadotropin releasing hormone agonists (GnRHa) for treatment of CCPP is usually restricted to 6-9 months, limiting their efficacy. There is limited information regarding safety and efficacy with longer-term use. The aim of this study is to examine the safety and efficacy of long-term (24 months) pituitary down-regulation with the GnRHa (Triptorelin SR) with add-back therapy (ABT) using Tibolone for symptom relief in women with CCPP. METHODS: A single-arm, prospective clinical trial at a Tertiary University Teaching Hospital of 27 patients receiving Triptorelin SR (11.25 mg) and Tibolone (2.5 mg). Outcomes measures were the safety of treatment assessed by clinical examination, haematological markers, liver and renal function tests and bone mineral density (BMD) at 12, 18 and 24 months as well as at 6 months post-treatment. Pain and health-related quality of life (HR-QoL) assessed using the endometriosis health profile (EHP-30) and chronic pain grade (CPG) questionnaires. RESULTS: There was no evidence for any significant harmful effects on any of the measured haematological, renal or liver function tests. Although results regarding the effect on BMD are not conclusive there is an increased risk of development of osteopaenia after 12 months of treatment. Pain and HRQoL assessments showed significant improvement during medication, but with deterioration after treatment cessation. CONCLUSION: Long- term Triptorelin plus Tibolone add-back therapy in women suffering from CCPP does not appear to be associated with significant serious adverse events apart from the possibility of deterioration in the BMD that needs to be monitored. This mode of therapy appears to be effective in pain relief and in improving quality of life over a 24-month period. TRIAL REGISTRATION: Clinical trials database NCT00735852

Do South Asian women with PCOS have poorer health-related quality of life than Caucasian women with PCOS? A comparative cross-sectional study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common chronic endocrine disorder affecting women of reproductive age. This study aimed to compare the HRQoL of South Asian and white Caucasian women with PCOS, given that it is particularly common among women of South Asian origin and they have been shown to have more severe symptoms. METHODS: The Polycystic Ovary Syndrome Questionnaire (PCOSQ) and the Short Form-36 (SF-36) were administered in a cross-sectional survey to 42 South Asian and 129 Caucasian women diagnosed with PCOS recruited from the gynaecology outpatient clinics of two university teaching hospitals in Sheffield and Leeds. Additional clinical data was abstracted from medical notes. Normative data, collected as part of the Oxford Health and Lifestyles II survey, was obtained to compare SF-36 results with ethnically matched women from the general UK population. Using the SF-36, normative HRQoL scores for women of South Asian origin were lower than for Caucasian women. Given this lower baseline we tested whether the same relationship holds true among those with PCOS. RESULTS: Although HRQoL scores for women with PCOS were lower than normative data for both groups, South Asian women with PCOS did not have poorer HRQoL than their Caucasian counterparts. For both the SF-36 and PCOSQ, mean scores were broadly the same for both Asian and Caucasian women. For both groups, the worst two HRQoL domains as measured on the PCOSQ were 'infertility' and 'weight', with respective scores of 35.3 and 42.3 for Asian women with PCOS compared to 38.6 and 35.4 for Caucasian women with PCOS. The highest scoring domain for South Asian women with PCOS was 'menstrual problems' (55.3), indicating best health, and was the only statistically significant difference from Caucasian women (p = 0.01). On the SF-36, the lowest scoring domain was 'Energy & Vitality' for Caucasian women with PCOS, but this was significantly higher for Asian women with PCOS (p = 0.01). The best health status for both groups was 'physical functioning', although this was significantly lower for South Asian women with PCOS (p = 0.005). Interestingly, only two domains differed significantly from the normative data for the Asian women with PCOS, while seven domains were significantly different for the Caucasian women with PCOS compared to their normative counterparts. CONCLUSIONS: The HRQoL differences that exist between South Asian and Caucasian women in the general population do not appear to be replicated amongst women with PCOS. PCOS reduces HRQoL to broadly similar levels, regardless of ethnicity and differences in the normative baseline HRQoL of these groups

The Impact in Older Women of Ovarian FMR1 Genotypes and Sub-Genotypes on Ovarian Reserve

We recently associated ovarian FMR1genotypes and sub-genotypes with distinct ovarian aging patterns. How they impact older females is, however, unknown. We, therefore, investigated 217 consecutive first in vitro fertilization (IVF) cycles in women >40 assessing oocyte yields, stratified for better (anti-Müllerian hormone, AMH >1.05 ng/mL) or poorer (AMH≤1.05 ng/mL) functional reserve (FOR)). Mean age was 42.4±2.0 years, mean AMH 0.76±0.92 ng/mL and mean oocyte yield 5.3±5.4. Overall, and in women with better FOR, FMR1 did not affect oocyte yields. With poorer FOR (AMH≤1.05 ng/mL) women with het-norm/high, however, demonstrated higher oocyte yields (5.0±3.8) than those with het-norm/low sub-genotype 3.1±2.5; P = 0.03), confirmed after log conversion. Known associated with low FOR at young age, het-norm/high, thus, appears to preserve FOR into older age, and both het sub-genotypes appear to expand female reproductive lifespan into opposite directions

Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses

OBJECTIVE: The purpose of this analysis was to develop a population pharmacokinetic model for a novel recombinant human follicle-stimulating hormone (FSH) (FE 999049) expressed from a human cell line of foetal retinal origin (PER.C6(®)) developed for controlled ovarian stimulation prior to assisted reproductive technologies.METHODS: Serum FSH levels were measured following a single subcutaneous FE 999049 injection of 37.5, 75, 150, 225 or 450 IU in 27 pituitary-suppressed healthy female subjects participating in this first-in-human single ascending dose trial. Data was analysed by nonlinear mixed effects population pharmacokinetic modelling in NONMEM 7.2.0.RESULTS: A one-compartment model with first-order absorption and elimination rates was found to best describe the data. A transit model was introduced to describe a delay in the absorption process. The apparent clearance (CL/F) and apparent volume of distribution (V/F) estimates were found to increase with body weight. Body weight was included as an allometrically scaled covariate with a power exponent of 0.75 for CL/F and 1 for V/F.CONCLUSIONS: The single-dose pharmacokinetics of FE 999049 were adequately described by a population pharmacokinetic model. The average drug concentration at steady state is expected to be reduced with increasing body weight

Long term costs and effects of reducing the number of twin pregnancies in IVF by single embryo transfer: the TwinSing study

Contains fulltext : 87274.pdf (publisher's version ) (Open Access)BACKGROUND: Pregnancies induced by in vitro fertilisation (IVF) often result in twin gestations, which are associated with both maternal and perinatal complications. An effective way to reduce the number of IVF twin pregnancies is to decrease the number of embryos transferred from two to one. The interpretation of current studies is limited because they used live birth as outcome measure and because they applied limited time horizons. So far, research on long-term outcomes of IVF twins and singletons is scarce and inconclusive. The objective of this study is to investigate the short (1-year) and long-term (5 and 18-year) costs and health outcomes of IVF singleton and twin children and to consider these in estimating the cost-effectiveness of single embryo transfer compared with double embryo transfer, from a societal and a healthcare perspective. METHODS/DESIGN: A multi-centre cohort study will be performed, in which IVF singletons and IVF twin children born between 2003 and 2005 of whom parents received IVF treatment in one of the five participating Dutch IVF centres, will be compared. Data collection will focus on children at risk of health problems and children in whom health problems actually occurred. First year of life data will be collected in approximately 1,278 children (619 singletons and 659 twin children). Data up to the fifth year of life will be collected in approximately 488 children (200 singletons and 288 twin children). Outcome measures are health status, health-related quality of life and costs. Data will be obtained from hospital information systems, a parent questionnaire and existing registries. Furthermore, a prognostic model will be developed that reflects the short and long-term costs and health outcomes of IVF singleton and twin children. This model will be linked to a Markov model of the short-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies to enable the calculation of the long-term cost-effectiveness. DISCUSSION: This is, to our knowledge, the first study that investigates the long-term costs and health outcomes of IVF singleton and twin children and the long-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies

A review of the human vs. porcine female genital tract and associated immune system in the perspective of using minipigs as a model of human genital Chlamydia infection

International audienceAbstractSexually transmitted diseases constitute major health issues and their prevention and treatment continue to challenge the health care systems worldwide. Animal models are essential for a deeper understanding of the diseases and the development of safe and protective vaccines. Currently a good predictive non-rodent model is needed for the study of genital chlamydia in women. The pig has become an increasingly popular model for human diseases due to its close similarities to humans. The aim of this review is to compare the porcine and human female genital tract and associated immune system in the perspective of genital Chlamydia infection. The comparison of women and sows has shown that despite some gross anatomical differences, the structures and proportion of layers undergoing cyclic alterations are very similar. Reproductive hormonal cycles are closely related, only showing a slight difference in cycle length and source of luteolysing hormone. The epithelium and functional layers of the endometrium show similar cyclic changes. The immune system in pigs is very similar to that of humans, even though pigs have a higher percentage of CD4+/CD8+ double positive T cells. The genital immune system is also very similar in terms of the cyclic fluctuations in the mucosal antibody levels, but differs slightly regarding immune cell infiltration in the genital mucosa - predominantly due to the influx of neutrophils in the porcine endometrium during estrus. The vaginal flora in Göttingen Minipigs is not dominated by lactobacilli as in humans. The vaginal pH is around 7 in Göttingen Minipigs, compared to the more acidic vaginal pH around 3.5–5 in women. This review reveals important similarities between the human and porcine female reproductive tracts and proposes the pig as an advantageous supplementary model of human genital Chlamydia infection