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Infertility female [keywords]
- Cost of fertility treatment and live birth outcome in women of different ages and BMI. [JOURNAL ARTICLE]
- Hum Reprod 2014 Jul 24.
What is the impact of different age and BMI groups on total investigation and treatment costs in women attending a secondary/tertiary care fertility clinic?Women in their early to mid-30s and women with normal BMI had higher cumulative investigation and treatment costs, but also higher probability of live birth.Female age and BMI have been used as criteria for rationing publically funded fertility treatments. Population-based data on the costs of investigating and treating infertility are lacking.A retrospective cohort study of 2463 women was conducted in a single secondary/tertiary care fertility clinic in Aberdeen, Scotland from 1998 to 2008.Participants included all women living in a defined geographical area referred from primary care to a specialized fertility clinic over an 11-year period. Women were followed up for 5 years or until live birth if this occurred sooner. Mean discounted cumulative National Health Service costs (expressed in 2010/2011 GBP) of fertility investigations, treatments (including all types of assisted reproduction), and pregnancy (including delivery episode) and neonatal admissions were calculated and summarized by age (≤30, 31-35, 36-40, >40 years) and BMI groupings (<18.50, 18.50-24.99 (normal BMI), 25.00-29.99, 30.00-34.99, ≥35.00 kg/m(2)). Further multivariate modelling was carried out to estimate the impact of age and BMI on investigation and treatment costs and live birth outcome, adjusting for covariates predictive of the treatment pathway and live birth.Of the 2463 women referred, 1258 (51.1%) had a live birth within 5 years, with 694 (55.1%) of these being natural conceptions. The live birth rate was highest among women in the youngest age group (64.3%), and lowest in those aged >40 years (13.4%). Overall live birth rates were generally lower in women with BMI >30 kg/m(2). The total costs of investigations were generally highest among women younger than 30 years (£491 in those with normal BMI), whilst treatment costs tended to be higher in 31-35 year olds (£1,840 in those with normal BMI). Multivariate modelling predicted a cost increase associated with treatment which was highest among women in the lowest BMI group (across all ages), and also highest among women aged 31-35 years. The increase in the predicted probability of live birth with exposure to treatment was consistent across age and BMI categories (∼10%), except in the oldest age group where a slightly smaller increase in the probability of live birth was observed. The ratio of increased costs to the increased probability of live birth in women who were treated increased markedly in women over the age of 40 years, but tended to fall as BMI increased within all age groups.Our results, based on retrospective observational data from a single centre, have limited generalizability and are not free from clinician and clinic selection bias which can influence the choice of treatments as well as their costs.Spontaneous live birth rates were particularly high in younger women with unexplained infertility, suggesting that expectant management is a reasonable option in this group. The policy of not over-investigating older women and offering early treatment where appropriate still incurred the highest costs per additional live birth associated with treatment, owing to the lower probability of treatment success. The increased additional cost for each live birth associated with treatment for women with decreasing BMI across all age groups, suggests that it may be possible to identify a more targeted approach to treatment.This study was partly funded by an NHS endowment grant (Grant Number 12/48) and D.J.M. by a Chief Scientist Office Postdoctoral Fellowship (Ref PDF/12/06). There are no conflicts of interest to declare.
- Clinical prediction models to inform individualized decision-making in subfertile couples: a stratified medicine approach. [REVIEW]
- Hum Reprod 2014 Jul 24.
Infertility is defined as failure to conceive after 1 year of unprotected intercourse. This dichotomization into fertile versus infertile, based on lack of conception over 12-month period, is fundamentally flawed. Time to conception is strongly influenced by factors such as female age and whilst a minority of couples have absolute infertility (sterility), many are able to conceive without intervention but may take longer to do so, reflecting the degree of subfertility. This natural variability in time to conception means that subfertility reflects a prognosis rather than a diagnosis. Current clinical prediction models in fertility only provide individualized estimates of the probability of either treatment-independent pregnancy or treatment-dependent pregnancy, but do not take account of both. Together, prognostic factors which are able to predict natural pregnancy and predictive factors of response to treatment would be required to estimate the absolute increase in pregnancy chances with treatment. This stratified medicine approach would be appropriate for facilitating personalized decision-making concerning whether or not to treat subfertile patients. Published models are thus far of little value for decisions regarding when to initiate treatment in patients who undergo a period of, ultimately unsuccessful, expectant management. We submit that a dynamic prediction approach, which estimates the change in subfertility prognosis over the course of follow-up, would be ideally suited to inform when the commencement of treatment would be most beneficial in those undergoing expectant management. Further research needs to be undertaken to identify treatment predictive factors and to identify or create databases to allow these approaches to be explored. In the interim, the most feasible approach is to use a combination of previously published clinical prediction models.
- The T657C polymorphism on the SYCP3 gene is associated with recurrent pregnancy loss. [JOURNAL ARTICLE]
- J Assist Reprod Genet 2014 Jul 25.
SYCP3 (Sinaptonemal complex protein 3) plays a critical role in pairing and recombination of homologous chromosomes in meiosis 1. It has been shown that lack of this gene leads to infertility in male and weakened fertility in female mice. In a case-control study, we investigated the SYCP3T657C polymorphism in the genome of 100 Iranian women with recurrent pregnancy losses of unknown causes as well as 100 control samples of normal fertile women having at least one healthy child. The general aim of our study was to determine whether there is a relationship between genetic changes in the SYCP3 gene and recurrent pregnancy loss in human or not. Frequency of the heterozygous genotype and mutated allele C were significantly higher in women with recurrent pregnancy losses (P-value < 0.005). Our findings suggest that the T657C polymorphism of the SYCP3 gene is possibly associated with recurrent pregnancy loss of unknown cause in human.
- Precocious puberty in a patient with mosaic Turner syndrome. [Journal Article]
- Genet Couns 2014; 25(2):183-7.
Turner syndrome (TS) is one of the most common human chromosome abnormalities, occurring in approximately 1:2500 live female births. Short stature, ovarian dysgenesis and infertility are clinical hallmarks in the majority of patients with TS. The incidence of spontaneous puberty in TS is reported to be about one third. Precocious puberty in TS patients is very rare. Herein, we report precocious puberty in a case with TS.
- Fertility preservation program before ovarotoxic oncostatic treatments: role of the psychological support in managing emotional aspects. [JOURNAL ARTICLE]
- Gynecol Endocrinol 2014 Jul 23.:1-3.
Abstract Fertility preservation programs (FPPs) based on oocyte or ovarian tissue cryostorage may be offered to women facing oncostatic treatments at risk of precocious ovarian insufficiency. The way in which FPPs are presented to patients affects their decision to join them. We studied herein 48 young women to whom a FPP was proposed, aiming at clarifying the emotional aspects involved. A psychologist attended the consultations in which the FPP was offered to patients; at the end of the talk, a questionnaire was administered and a semi-structured interview was carried out. Finally, the STAI test was administered to measure trait (TAI) and state (SAI) anxiety, both immediately after consultation, and later on, when patients returned home. We observed that the possibility to join a FPP implied important emotional aspects, and that the presence of a psychologist was helpful to integrate technical information and emotions as well as to reduce trait and state anxiety levels. Our study suggests that the presence of a psychologist during the meeting in which a FPP is offered improves communication between doctors and patients, and helps these women to get a full awareness before choosing to join the FPP.
- Over-expression of Corticotropin Releasing Factor in the Central Nucleus of the Amygdala Advances Puberty and Disrupts Reproductive Cycles in Female Rats. [JOURNAL ARTICLE]
- Endocrinology 2014 Jul 22.:en20141339.
Prolonged exposure to environmental stress activates the hypothalamic-pituitary-adrenal (HPA) axis and generally disrupts the hypothalamic-pituitary-gonadal (HPG) axis. As corticotropin-releasing factor (CRF) expression in the central nucleus of the amygdala (CeA) is a key modulator in adaptation to chronic stress, and central administration of CRF inhibits the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator, we tested the hypothesis that over-expression of CRF in the CeA of female rats alters anxiety behaviour, dysregulates the HPA axis response to stress, changes pubertal timing and disrupts reproduction. We used a lentiviral vector to increase CRF expression site specifically in the CeA of pre-weaning (postnatal day 12) female rats. Over-expression of CRF in the CeA increased anxiety-like behavior in peripubertal rats shown by a reduction in time spent in the open arms of the elevated plus maze and a decrease in social interaction. Paradoxically, puberty onset was advanced, but followed by irregular estrous cyclicity and an absence of spontaneous preovulatory LH surges associated with proestrous vaginal cytology in rats over-expressing CRF. Despite the absence of change in basal or stress (lipopolysaccharide or restraint) induced corticosterone secretion, over-expression of CRF in the CeA significantly decreased lipopolysaccharide, but not restraint, stress-induced suppression of pulsatile LH secretion in post pubertal ovariectomized rats, indicating a differential stress responsivity of the GnRH pulse generator to immunological stress and a potential adaptation of the HPA axis to chronic activation of amygdaloid CRF. These data suggest that the expression profile of this key limbic brain CRF system might contribute to the complex neural mechanisms underlying the increasing incidence of early onset of puberty on the one hand and infertility on the other attributed to chronic stress in modern human society.
- Pigment epithelium derived factor (PEDF) in the reproductive system. [JOURNAL ARTICLE]
- Reproduction 2014 Jul 21.
The physiological function of the female reproductive organs is hormonally controlled. In each cycle the reproductive organs undergo tissue modifications that are accompanied by formation and destruction of blood vessels. Proper angiogenesis requires an accurate balance between stimulation and inhibition of angiogenesis, maintained by pro- and anti-angiogenic factors. As with many other tissues, vascular endothelial growth factor (VEGF) appears to be one of the major pro-angiogenic factors in the female reproductive organs. Pigment epithelium-derived factor (PEDF) is a non-inhibitory member of the serine protease inhibitors (serpin) superfamily, possessing potent physiologic anti-angiogenic activity that negates VEGF activity. The anti-angiogenic effect of PEDF has been extensively investigated in the eye and in cancer, demonstrating its role in decreasing abnormal neovascularization, mainly by inhibiting the stimulatory activity of several strong pro-angiogenic factors, including VEGF. This review summarizes the function of PEDF in the reproductive system, showing its hormonal regulation and its anti-angiogenic activity. Furthermore, some pathologies of the female reproductive organs, including endometriosis, ovarian hyperstimulation syndrome (OHSS), polycystic ovary syndrome (PCOS), and others, are associated with a faulty angiogenic process; therefore, this review illuminates the role of PEDF in their pathogenesis and treatment. Collectively, we can conclude that although PEDF seems to play an essential role in the physiology and pathophysiology of the reproductive system its full role and mechanism of action still need to be illustrated.
- Laparoscopic Dissection and Anatomy of Sacral Nerve Roots and Pelvic Splanchnic Nerves. [JOURNAL ARTICLE]
- J Minim Invasive Gynecol 2014 Jul 15.
to demonstrate the technique of laparoscopic dissection for identification of sacral nerve roots and pelvic splanchnic nerves.case report.Classification: Canadian Task Force Classification III.private practice hospital in São Paulo, Brazil.31-years old female patient with suspected iatrogenic and/or compression of sacral nerve roots. She had debilitating pelvic, gluteal and perineal unilateral left pain (score 8, pain scale 0-10), and primary infertility with one previous failed IVF attempt. Surgical history included laparoscopic excision of endometriosis 10 months before the procedure, and a left ooforoplasty during adolescence for a benign neoplasm.Standard 4-puncture laparoscopy was established. Peritoneum of the left pelvic sidewall was resected to eradicate eventual residual endometriosis. This also allowed for the identification of uterine vessels, including the deep uterine vein, which is the limit between the pars vascularis (superiorly) and pars nervosa (inferiorly) in the uterine broad ligament. Surgery was based in the LANN (laparoscopic neuronavigation) technique, previously described by one of the authors. For identification of the sacral roots, dissection began medial to the ureter and lateral to the uterosacral ligament. Okabayashi's pararectal space was developed as deepest as possible by blunt dissection in avascular spaces. Hemostasis was performed with 5-mm bipolar forceps, and harmonic energy was not used. The hypogastric fascia was entered from medial to lateral, and the piriformis muscle was identified. The sacral nerve root S1 was identified lying over it. Dissection then proceeded caudally, and sacral roots S2 and S3 were sequentially identified. Small and delicate fibers forming the pelvic splanchnic nerves were isolated emerging from sacral roots S2 and S3. Other nerve fibers were identified caudally, probably representing pelvic splanchnic nerves emerging from S4.surgery lasted 70 minutes and bleeding was minimal. There was no suspected compression or iatrogenic injury identified. Patient was discharged in the following day. After 8 months of follow-up, she had partial recovery of pain (score 5, pain scale 0 to 10), and another failed IVF attempt, attributed to unsatisfactory quality of the embryos. There were no symptoms or dysfunctions attributable to manipulation of the nerves.laparoscopy is a useful tool to identify sacral roots and pelvic splanchnic nerves for suspected diseases. Its applications in the field of neuropelveology can be expanded by proper knowledge and training.
- Exogenous Leptin Administered Intramuscularly Induces Sex Hormone Disorder and Ca Loss via Downregulation of Gnrh and PI3K Expression. [JOURNAL ARTICLE]
- Exp Anim 2014 Jul 22.
Obesity is a public health problem that increases the risk of metabolic disease, infertility, and other chronic health problems. The present study aimed to develop a new rat model for sex hormone disorder with overweight and Ca loss by intramuscular injection of exogenous leptin (LEP). Thirty female Sprague-Dawley (SD) rats (40 days old) were injected thrice intramuscularly with LEP or keyhole limpet hemocyanin immunogen. The following analyses were performed to determine the development of appetite, overweight, reproductive related-hormones, and calcium (Ca)/phosphorus (Pi) in SD rats: measurement of Lee's index, body weight, food intake; serum Ca, Pi, and hormone tests by enzyme-linked immunosorbent analysis; histological analysis of abdominal fat; real-time polymerase chain reaction analysis of neuropeptide Y, pro-opiomelanocortin, gonadotropin-releasing hormone (Gnrh) mRNA, and gonadotropin-releasing hormone receptor (Gnrhr) mRNA expression; and western blotting analysis of enzyme phosphatidylinositol-3-kinase (PI3K). Rats injected with LEP immunogen displayed significantly increased body weight, food intake, Lee's index, serum LEP, serum cortisol, fat deposition in the abdomen, and decreased hormones including follicle stimulating hormone, luteinizing hormone, estradiol, cholecystokinin, and Ca. Exogenous LEP administered intramuscularly also downregulate Gnrh and PI3K. In conclusion, exogenous LEP administered intramuscularly is a novel animal model for sex hormones disorder with overweight and Ca loss in SD rats. The downregulation of PI3K and Gnrh may be involved in the development of this animal model.
- Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis. [Journal Article]
- Nat Commun 2014.:4478.
Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel β3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans.