BACKGROUND

The roles of cell proliferation and genomic instability in endometriosis are highly debated aspects of the pathogenesis of this disease. Aurora A and B kinases play different important roles in cell cycle control and genomic instability and have never been studied in endometriosis. The aim of this study was to compare the expression levels of Aurora kinases, Ki-67 and hormone receptor in endometriotic tissue (ET) and normal endometrium.

METHODS

We retrospectively analysed 438 samples obtained from 194 patients affected by endometriosis and 28 samples from 28 patients with normal endometrium, which were all collected by the Pathology Department and Gynecologic Clinic of the University Hospital of Udine. A tissue microarray model was constructed to use immunohistochemistry to analyse the expression of Aurora A and B kinases, Ki-67 and the estrogen and progesterone receptors in ET and normal endometrium.

RESULTS

Aurora A and B kinases were expressed at a very low level in the majority of endometriosis core biopsies. Aurora A and B kinases, Ki-67 and the estrogen and progesterone receptors were expressed at a higher level in the proliferative endometrium than in the secretory endometrium and in ovarian and non-ovarian ET (P< 0.05). Additionally, Aurora B kinase, Ki-67 and the estrogen and progesterone receptors were more highly expressed in non-ovarian than ovarian ET (P< 0.05).

CONCLUSIONS

Considering the low expression levels of Aurora A and B kinases in the majority of endometriosis core biopsies, the growth and survival of endometrial tissue outside the uterus cannot be explained by deregulation of this pathway. The analysed ectopic endometrium protein expression pattern resembled that of the secretory endometrium, and markers of proliferation and hormone receptors were expressed at lower levels in ovarian than in non-ovarian ET. The low level of hormone receptors and the consequent low levels of proliferation markers in ovarian ETs may be due to down-regulation by the ovary's hormone milieu.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

In view of the discrepancies about the GnRH antagonist (GnRH-ant) ovarian stimulation protocols having some potential advantages compared with the GnRH agonist (GnRH-a) protocols in poor ovarian responders IVF/ICSI, a meta-analysis of the published data was performed to compare the efficacy of GnRH-ant versus GnRH-a protocols for ovarian stimulation in IVF poor response patients.

METHODS

We searched for all published articles indexed in MEDLINE (1950–2010), EMBASE (1974–2010) and China National Knowledge Infrastructure (CNKI, 1994–2010). Any randomized controlled study that compared the GnRH-ant with GnRH-a in ovarian stimulation protocols for poor responders undergoing IVF/ICSI was included, and data were extracted independently by two reviewers. The searches yielded 64 articles, from which 14 studies met the inclusion criteria. We performed this meta-analysis involving 566 IVF patients in a GnRH-ant protocol group and 561 patients in a GnRH-a protocol group with Review Manager 4.2 software. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence intervals (CIs) were used to evaluate dichotomous and continuous data, respectively.

RESULTS

Fourteen eligible studies were included in this meta-analysis. GnRH-ant protocols resulted in a statistically significantly lower duration of stimulation compared with GnRH-a protocols (P = 0.04; WMD: –1.88, 95% CI: –3.64, –0.12), but there was no significant difference in the number of oocytes retrieved (P = 0.51; WMD: –0.17, 95% CI –0.69, 0.34) or the number of mature oocytes retrieved (P = 0.99; WMD: –0.01, 95% CI: –1.14, 1.12). Moreover, no significant difference was found in the cycle cancellation rate (CCR, P = 0.67; OR: 1.01, 95% CI: 0.71–1.42) or clinical pregnancy rate (CPR, P = 0.16; OR: 1.23, 95% CI: 0.92, 1.66).

CONCLUSIONS

Clear advantage was gained in duration of stimulation with GnRH-ant in poor ovarian responders undergoing IVF, although there was no statistical difference in the number of oocytes retrieved, the number of mature oocytes retrieved, the CCR and CPR between GnRH-ant and GnRH-a protocols. These results may be helpful to our clinical practice. However, further controlled randomized prospective studies with larger sample sizes are needed.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Smooth muscle cells (SMC) are common components of endometriotic lesions. SMC have been characterized previously in peritoneal, ovarian and deep infiltrating endometriotic lesions and adenomyosis. The aim of this retrospective study was to investigate the extent of differentiation in endometriosis-associated SMC (EMaSMC) in peritoneal endometriotic lesions.

METHODS

We obtained biopsies from peritoneal endometriotic lesions (n= 60) and peritoneal sites distant from the endometriotic lesion (n= 60), as well as healthy peritoneum from patients without endometriosis (control tissue, n= 10). These controls were hysterectomy specimens from patients without endometriosis or adenomyosis. Histopathological examination of peritoneal specimens using antibodies against oxytocin receptor (OTR), vasopressin receptor (VPR), smooth muscle myosin heavy chain (SM-MHC), estrogen receptor (ER) or progesterone receptor (PR) was performed. To identify SMC and their level of differentiation, antibodies for smooth muscle actin desmin and caldesmon were used.

RESULTS

SMC were detected in all endometriotic lesions. SMC were more abundant in unaffected peritoneum of women with endometriosis (38%) compared with women without endometriosis (6%; P < 0.0001). Depending on the level of differentiation, SMC stained for SM-MHC, OTR, VPR, ER and PR. OTR was only detected in fully differentiated SMC.

CONCLUSIONS

Identification of OTR, VPR, ER and PR leads to the hypothesis that the EMaSMC might be functionally active and possibly involved in the generation of pain associated with endometriosis.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Serous, endometrioid, clear cell and mucinous histotypes are the most common epithelial ovarian cancer. Most serous cancers appear to originate from precursor lesions at the fimbriated tubal end, whereas most endometrioid and clear cell cancers seem to derive from atypical endometriosis. Data regarding hormonal factors and associated gynaecologic conditions were critically analysed with the objective of defining a carcinogenic model for sporadic epithelial ovarian cancer complying with epidemiologic and pathologic findings. Oral contraceptives and tubal ligation substantially reduce the risk of serous, endometrioid and clear cell subgroups, but have no significant effect on mucinous tumours, which probably follow a different oncogenic pathway. We hypothesize that serous, endometrioid and clear cell cancers share a common pathogenic mechanism, i.e. iron-induced oxidative stress derived from retrograde menstruation. Fimbriae floating in bloody peritoneal fluid are exposed to the action of catalytic iron and to the genotoxic effect of reactive oxygen species, generated from haemolysis of erythrocytes by pelvic macrophages. This would explain the distal site of tubal intraepithelial neoplasia. Collection of blood inside endometriomas would lead to the same type of genotoxic insult on gonadal endometrial implants. This would explain why endometriosis-associated cancers develop much more frequently in the ovary than at extragonadal sites. In women not seeking conception, bilateral salpingectomy could be advised whenever planning surgery for independent indications, thus possibly reducing cancer risk, while preserving ovarian function. The use of oral contraceptives should be favoured for prolonged periods of time, especially in women with endometriosis, a population at doubled risk of gonadal malignancy.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Prior studies have documented increased risks to the offspring of IVF singletons that result from a vanished twin pregnancy. We aim to investigate the effect on perinatal outcomes of having an early vanished triplet in IVF twins.

METHODS

This is a retrospective cohort study of twins from a large academic IVF practice. Multivariate analysis was performed to examine the perinatal risks—including small for gestational age (SGA), low-birthweight (LBW), preterm delivery and early preterm delivery—in twins that resulted from an early vanished triplet compared with twins without a vanished embryo.

RESULTS

Of 829 IVF twin deliveries, 59 were a result of vanished triplet pregnancies (7.1%). There was no significant increase in SGA, LBW or delivery <37 weeks in the vanished triplets compared with other twins; however, the risk of early preterm birth (<32 weeks) was significantly higher (OR 3.09, 95% CI 1.63–5.87) and the length of gestation of these pregnancies was on average 1.5 weeks shorter (P< 0.01). In addition, the unadjusted mean birthweight was lower by nearly 200 g in the vanished triplet pregnancies (P< 0.01).

CONCLUSIONS

IVF twin pregnancies with a vanished triplet are at an increased risk for early preterm birth compared with other twin pregnancies. These pregnancies should be recognized at higher risk for early preterm birth and considered for increased obstetrical monitoring. A significant limitation of this study is that the cause for preterm birth was unknown.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Hyper-activated motility (HAM) is part of the sperm capacitation process, which is necessary for fertilization. In this study, we investigated the effect of visible light on sperm motility and hyperactivation and evaluated pathways mediating these effects.

METHODS

Human sperm (1 x 10⁷ cells/ml) in capacitation media were irradiated for 3 min with 40 mW/cm² visible light (400–800 nm with maximum energy at 600 nm). Sperm motility was assessed and analyzed by computer-assisted sperm analysis. The involvement of sperm capacitation factors was investigated as follows. The generation of reactive oxygen species (ROS) was measured using 20,70-dichlorofluorescein diacetate. Protein kinase A (PKA) and sarcoma protein kinase (Src) activity were measured using western blot analysis and inhibited using 50 µM H89 and 10 µM PP2, respectively. Soluble adenlyl cyclase was inhibited using 20 µM 2-OH-Estradiol. The intracellular concentration of free Ca²⁺ was assessed using the fluorescent calcium indicator, Fluo-4/AM. Sperm DNA fragmentation was determined using the sperm chromatin dispersion test.

RESULTS

Light irradiation of human sperm caused a significant increase in hyper-HAM but not total motility. The production of ROS and activation of soluble adenylyl cyclase and PKA mediated the effect of light on HAM. Light irradiation also activated Src, and inhibition of Src significantly reduced the effect of light on HAM. Light irradiation caused a rapid increase in intracellular Ca²⁺ concentration and the increase in HAM was significantly reduced when voltage-dependent-Ca²⁺-channel activity was blocked or when Ca²⁺-deficient medium was used.

CONCLUSIONS

Light irradiation of human sperm for a short time causes a significant increase in HAM in a mechanism mediated by ROS production, activation of PKA, Src and Ca²⁺ influx.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Despite the increasing use of intravenous immunoglobulin (IVIG) in obstetrics, information on its pharmacokinetics and optimal dosing during each trimester pregnancy is lacking. The aim of this study was to characterize IVIG pharmacokinetics in pregnant women with a history of idiopathic secondary recurrent miscarriage or obstetrical antiphospholipid syndrome and to make dosing recommendations by comparing serum immunoglobulin G (IgG) concentrations in women receiving IVIG to placebo controls, before and during pregnancy.

METHODS

Women enrolled in an IVIG trial for idiopathic secondary recurrent miscarriage (n = 25) or an IVIG study for obstetrical antiphospholipid syndrome (n = 10); 22 received IVIG 0.5–1.0 g/kg and 13 received the equivalent volume of saline, every 4 weeks from pre-pregnancy until 18–20 weeks of gestation, with dosing adjusted for her weight prior to each infusion. Serum IgG concentrations were measured by rate nephelometry before and 0.5 h, and 1, 2, 3 and 4 weeks following an infusion. Sampling was performed pre-pregnancy and in the first and second trimesters.

RESULTS

Area under the curve (AUC) did not differ significantly within the IVIG group between the three sampling periods. Estimated contributions of IVIG [calculated as mean AUC (IVIG group) minus mean AUC (control group)] were 4890.8 g h/l pre-pregnancy, 5591.4 g h/l first trimester and 4755.1 g h/l second trimester (P> 0.05, non-significant). For the IVIG 0.5 and 1.0 g/kg subgroups, the overall estimated contribution of exogenous IVIG was ~4000 and ~6400 g h/l, respectively.

CONCLUSIONS

With a weight-adjusted dosage of IVIG, drug exposure, based on AUC calculations, was maintained at the pre-pregnancy level. Therefore, we recommend a weight-adjusted dosage of IVIG during the first and second trimesters.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Uterine natural killer (uNK) cells are a major source of cytokines and angiogenic growth factors (AGFs), with AGF levels decreasing and cytokine levels increasing with gestational age. The factors that regulate AGF and cytokine secretion are unclear but may involve interactions between uNK cells and extravillous trophoblast (EVT) cells. We hypothesize that uNK cell interaction with EVT cells alters their cytokine and AGF secretion.

METHODS

Ex vivo co-cultures of uNK cells with either EVT (irradiated or fresh) or villous cytotrophoblast (CTB; control cell type) cells isolated from the same patients at 8–10 or 12–14 weeks gestational age (n = 10 each group) were established. Co-cultures were established with either direct contact between the different cell types or with the cells separated by a 0.4 µm filter. AGFs and cytokines were measured in cell culture supernatants using multiplex analysis (FAST Quant) or ELISA.

RESULTS

Secretion of angiopoietin-1 (P< 0.006) and vascular endothelial growth factor-C (P< 0.001) by uNK cells was lower when these cells were co-cultured, either directly or indirectly, with both trophoblast cell types at both gestational ages tested compared with when cultured alone. In contrast, interleukin (IL)-6 (P < 0.0001), IL-8 (P < 0.0001) and transforming growth factor-β1 (P < 0.002) were decreased only in direct uNK/EVT and uNK/CTB co-culture conditions at 8–10 and 12–14 weeks gestational age.

CONCLUSIONS

AGF and cytokine secretion was reduced after co-culture of uNK cells and both EVT and CTB cells. It remains unclear whether uNK cell AGF and cytokine production was reduced after co-culture with trophoblast cells (EVT or CTB) or whether trophoblast cell (EVT or CTB) AGF and cytokine production was reduced after co-culture with uNK cells. Local production of AGFs and cytokines in the placental bed may be lowered when uNK cells come in direct contact with EVT cells.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

The involvement of biogenic monoamines in early (‘preneural’) embryogenesis has been well documented in lower vertebrates, but much less information is available about the role of these molecules in the earliest stages of development in mammals, including humans.

METHODS

Databases (PubMed, ISI Web of Knowledge and Scopus) were searched for studies relating to biogenic monoamines functioning in early embryos. The available data on the expression of histamine, serotonin and adrenergic receptors during mammalian preimplantation development were summarized, and the potential roles of biogenic monoamines in very early pregnancy were discussed.

RESULTS

The roles of biogenic monoamines in mammalian preimplantation embryo development can be diverse, depending on the embryo developmental stage, and the physiological status of the maternal organism. Several receptors for biogenic monoamines are expressed and biologically functional in cells of preimplantation embryos. Activation of histamine receptors can play a role in embryo implantation and trophoblast invasion. Activation of adrenergic and serotonin receptors can influence proliferation and survival of early embryonic cells.

CONCLUSIONS

Biogenic monoamines can play an important role in physiological conditions, contributing to embryo-maternal interactions, or can influence the early embryo under unfavorable or pathological conditions (e.g. in maternal stress, or in women taking certain antidepressants, anti-migraine or anti-ulcer drugs).

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

An enteric-coated levonorgestrel emergency contraceptive pill (E-LNG-ECP) is an improved formulation, in terms of side effects, which both dissolves and is absorbed in the intestine. Our aim was to evaluate the efficacy and safety of E-LNG-ECP as an over-the-counter (OTC) drug for emergency contraception (EC) in Chinese women.

METHODS

A Phase IV clinical trial was conducted in five family planning clinics in China. Women seeking EC within 72 h after unprotected sexual intercourse or contraceptive failure who met the inclusion criteria were recruited. The efficacy of contraception (primary end-point was pregnancy rate), side effects (i.e. safety) and the value of E-LNG-ECP for EC were investigated.

RESULTS

Of 2445 women (aged 15–48 years) who took E-LNG-ECP with follow-up to determine pregnancy, only five pregnancies (0.2%) occurred. The efficacy of contraception was 95.3%. In total, 6.5% of women reported at least one adverse event after taking E-LNG-ECP, and no serious adverse events were reported. Only four subjects (0.16%) reported vomiting. The incidence of menstrual cycle disturbance was 20.1% after taking E-LNG-ECP. Subjects who had previously taken ECPs (54.4% of these women) rated the acceptability of E-LNG-ECP at 9.36 (on a 10-point scale) higher (P<0.05) than the rating of other LNG-EC pills taken previously.

CONCLUSIONS

The study found that E-LNG-ECP was effective, safe and well tolerated as an OTC drug. However, an randomized controlled trial should be performed to compare standard LNG tablets with E-LNG-ECP.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Sam68, a member of the signal transduction and activation of RNA metabolism (STAR) family of RNA-binding proteins, has been previously implicated as an adaptor molecule in different signaling systems, including leptin receptor (LEPR) signaling. LEPR activation is known to stimulate JAK-STAT, MAPK and PI3K signaling pathways, thus mediating the biological effects of leptin in different cell types, including trophoblastic cells. We have recently found that leptin stimulation also promotes the overexpression and tyrosine phosphorylation of Sam68 in human trophoblastic JEG-3 cells, suggesting a role for Sam68 in leptin signaling and action in these cells. In the present work, we have studied the participation of Sam68 in the main signaling pathways activated by LEPR to increase growth and proliferation in trophoblastic JEG-3 cells.

METHODS

We used an antisense strategy to down-regulate Sam68 expression in these cells, and we studied LEPR signaling by immunoprecipitation and poly-U affinity precipitation and by analyzing phosphorylation levels of signaling proteins by immunoblot. The effect of leptin on protein synthesis and proliferation was studied by ³[H]-leucine and ³[H]-thymidine incorporation.

RESULTS

Sam68 knockdown impaired leptin activation of JAK-STAT, PI3K and MAPK signaling pathways in JEG-3 cells. We have also found that leptin-stimulated Sam68 tyrosine phosphorylation is dependent on JAK-2 activity, since the pharmacological inhibitor AG490 prevents the phosphorylation of Sam68 in JEG-3 cells. Finally, the trophic and proliferative effect of leptin in trophoblastic cells is dependent on Sam68 expression, since its down-regulation impaired the leptin-stimulated DNA and protein synthesis.

CONCLUSIONS

These data demonstrate that Sam68 participates in the main signaling pathways of LEPR to mediate the trophic and proliferative effect of leptin in human trophoblastic cells.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Catamenial pneumothorax and thoracic endometriosis (TE) are still under diagnosed. The purpose of this study is to increase the diagnostic accuracy for these conditions in patients with spontaneous pneumothorax and to identify their risk factors.

METHODS

We conducted a retrospective study on all consecutive women of reproductive age referred to our Centre for surgical treatment of spontaneous pneumothorax between July 2000 and January 2009.

RESULTS

The study population comprised 156 premenopausal women of whom 49 (31.4%) had catamenial and/or TE-related pneumothorax. Over a quarter of these 49 patients had a previous history of recurrent thoracic or scapular catamenial pain. They experienced their first pneumothorax episode at an older age (mean ± SD) (34.0 years ± 6.7) than women with idiopathic pneumothorax (28.7 ± 6.1 years, P < 0.001). Pelvic endometriosis was found in 51% of women with catamenial and/or TE-related pneumothorax. After adjustment for confounding factors by multiple logistic regression analysis, the results show that, infertility [odd ratio (OR) = 4.21, 95% confidence interval (CI) = 1.28–13.88] and a history of pelvic surgery with a uterine procedure and/or uterine scraping (OR = 2.85, 95% CI = 1.12–7.26) were the strongest predictors of catamenial and/or TE-related pneumothorax.

CONCLUSIONS

Infertility and uterine procedures are significantly associated with catamenial and/or TE-related pneumothorax. Scapular or thoracic pain during menses often precedes the occurrence of pneumothorax and is highly specific for the diagnosis of TE. Our results suggest that in women with pelvic endometriosis, these symptoms should be systematically investigated for an earlier diagnosis of TE.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Colorectal segmental resection is performed worldwide in a majority of women presenting with symptomatic deep endometriosis infiltrating the rectum. The aim of the present study was to investigate the pathophysiological mechanisms involved in post-operative digestive dysfunction.

METHODS

We selected patients managed by colorectal resection for rectal endometriosis, who had developed post-operative severe constipation and whose follow up was superior to 24 months. To assess the mechanisms involved in the pathogenesis of this complaint, we performed a step-by-step work up including: low digestive tract endoscopy, colonic transit time measurement and when appropriate anorectal manometry, electromyography and defecographic evaluation.

RESULTS

Five out of 25 (20%) patients, whose age ranged from 27 to 41 years, were investigated for severe post-operative terminal constipation. Four different mechanisms responsible for terminal constipation were identified: tight stenosis of the colorectal anastomosis, post-operative neurological sequelae, colonic intussusception through the colorectal anastomosis and transit constipation that developed post surgery.

CONCLUSIONS

Post-operative constipation is a frequent complaint in women managed by colorectal resection for rectal endometriosis. A multidisciplinary approach is mandatory as pathophysiologic mechanisms may vary and prove difficult to understand. The risk of post-operative bowel dysfunction following colorectal endometriosis must be taken into account whenever this technique is proposed in young women presenting with a benign disease such as deep endometriosis.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Laparoscopic segmental bowel resection and reanastomosis for endometriosis with colorectal wall invasion can be associated with high complication rates. This study was performed to test the hypothesis that this high complication rate can be prevented and combined with a good clinical outcome, following a multidisciplinary surgical approach.

METHODS

A retrospective cohort study of all patients with deep endometriosis and colorectal invasion treated by CO₂ laser laparoscopic radical excision between September 2004 and September 2006 (n = 45) to document the clinical outcome: complications, recurrence and fertility (life table analysis), pain, quality of life (QOL) and sexual function.

RESULTS

No immediate major post-operative complications requiring surgical reintervention were recorded. Gynaecological pain (P< 0.0001), sexual function (P< 0.03) and QOL (P< 0.0001), improved significantly after a median follow-up period of 27 (range: 16–40) months. Although five patients (11%) had a surgical reintervention, histologically proven recurrent endometriosis was observed in only two (4%), with a cumulative endometriosis recurrence rate of 2.2 and 4.4% after 1 and 3 years, respectively. Thirteen of 28 patients who wanted to become pregnant conceived after surgery. One patient delivered twice. These 14 pregnancies were achieved spontaneously (n = 9) or after IVF (n = 5). The cumulative pregnancy rate was 47% after 3 years.

CONCLUSION

Pain, sexual function and QOL improved significantly and were associated with a good fertility rate and a low complication and recurrence rate after a CO₂ laser laparoscopic radical excision of endometriosis with colorectal wall invasion combined with laparoscopic segmental bowel resection and reanastomosis.

Source:
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BACKGROUND

This study aims to quantify the non-health-care costs of endometriosis in a sample of Belgian patients over a 30-month period.

METHODS

A longitudinal study enrolled patients who underwent surgical treatment for endometriosis in University Hospitals Leuven. Self-reported patient questionnaires measured costs at 1 month prior to surgical treatment and at 6, 12, 18 and 24 months following treatment. The number of days of work absence was valued using gross monthly income to estimate costs of productivity loss. Analysis included patient expenditure on support with household activities. The costs per patient over 6 months were obtained by linear extrapolation.

RESULTS

Of 394 eligible patients, 180 participated in the study (response rate of 46%). The highest productivity loss was incurred during the 6 months preceding surgical treatment (1514 ± 2576) and the 6 months following treatment (2496 ± 4144). Mean costs dropped to 115–225 during the following 6-month periods. Similarly, costs of support with household activities peaked during the 6 months preceding surgical treatment (982 ± 908) and during the subsequent 6 months (981 ± 1085), after which they dropped to 500–675 during the following 6-month periods. Patients with severe endometriosis (Stage IV) (4943) had higher total non-health-care costs over the 30-month period than patients with minimal-to-moderate endometriosis (Stages I–III) (4510) (P = 0.048).

CONCLUSIONS

As our study did not include a control population of women without endometriosis, patients were asked to report non-health-care costs associated with endometriosis only. Results show that the highest non-health-care costs associated with endometriosis are incurred during the 6 months prior to and following surgical treatment.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Anti-Müllerian hormone (AMH) is increasingly used to quantify ovarian reserve, but it has not yet realized its full clinical potential in assisted reproduction technology. We investigated the possible benefits of using novel, stratified ovarian hyperstimulation protocols, tailored to individual AMH levels, compared with conventional stimulation.

METHODS

Retrospective data were collected from 769 women (first cycle of IVF, using fresh embryos), in a UK tertiary care unit: 346 women using conventional stimulation protocols; 423 women treated under new AMH-tailored protocols.

RESULTS

Embryo transfer rates increased significantly (79–87%: P= 0.002) after the introduction of AMH-tailored stimulation protocols. Pregnancy rate per cycle started and live birth rate also increased significantly compared with conventionally treated women (17.9–27.7%, P= 0.002 and 15.9–23.9%, P = 0.007, respectively). Moreover, in the AMH group, the incidence of the ovarian hyperstimulation syndrome (OHSS) fell significantly (6.9–2.3%, P = 0.002) and failed fertilization fell from 7.8 to 4.5%. The cost of fertility drug treatment fell by 29% per patient and the overall cost of clinical management of OHSS fell by 43% in the AMH group. GnRH antagonist protocols, introduced as part of AMH-tailored treatment, may have contributed to the observed improvements: however, within the AMH-tailored group, the live birth rate was not significantly different between agonist and antagonist-treated groups.

CONCLUSIONS

Although large, prospective, multicentre studies are indicated, we have clearly demonstrated that individualized, AMH-guided, controlled ovarian hyperstimulation protocols significantly improved positive clinical outcomes, reduced the incidence of complications and reduced the financial burden associated with assisted reproduction.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Endometriosis is still a highly underdiagnosed disease, and the current medical and surgical treatment of endometriosis is associated with a high recurrence rate. This study investigates the use of derivatives of the human antibody F8, specific to the alternatively spliced extra-domain A of fibronectin (Fn), for the imaging and treatment of endometriosis.

METHODS

Immunohistochemistry and immunofluorescence was used to evaluate antigen expression in endometriotic tissue of human endometriosis and of a syngeneic mouse model of the disease. The in vivo targeting performance of a fluorescent derivative of the F8 antibody was assessed by imaging mice with endometriosis using a near-infrared fluorescence imager, 24 h following i.v. injection of the antibody conjugate. Furthermore, the mouse model was used for therapy experiments using two recombinant F8-based immunocytokines [F8-interleukin-10 (IL10) and F8-IL2] or saline for the treatment groups.

RESULTS

A very strong vascular expression of splice isoforms of Fn and of tenascin-C was observed in human endometriotic lesions by immunohistochemistry and immunofluorescence techniques. After i.v. administration, a selective accumulation of the F8 antibody in endometriotic lesions could be observed in a syngeneic mouse model. These targeting data were used as a basis for therapy experiments with a pro-inflammatory (F8-IL2) and an anti-inflammatory (F8-IL10) cytokine fusion protein of the F8 antibody. The average lesion size in the F8-IL10 treatment group was clearly reduced compared with the saline control group and with the F8-IL2 group, for which no therapeutic effects were observed.

CONCLUSIONS

The F8 antibody targets endometriotic lesions in vivo in a mouse model of endometriosis and may be used for the non-invasive imaging of the disease and for the pharmacodelivery of anti-inflammatory cytokines, such as IL10.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

There are few systematic studies of the incidence of cross-border fertility care and even fewer reports of qualitative research with those undertaking treatment outside their country of origin. This paper reports findings from a qualitative study of UK residents with experience of cross-border care: the socio-demographic characteristics of UK travellers; their reasons for seeking treatment abroad; the treatments they sought; the destinations they chose and the outcomes of their treatment.

METHODS

Data regarding cross-border fertility treatment were collected from a purposive sample of 51 people by means of in-depth, semi-structured interviews between May 2009 and June 2010. Data were analysed using a systematic thematic coding method and also subjected to quantitative translation.

RESULTS

Patient motivations for travelling abroad are complex. A desire for timely and affordable treatment with donor gametes was evident in a high number of cases (71%). However, most people gave several reasons, including: the cost of UK treatment; higher success rates abroad; treatment in a less stressful environment and dissatisfaction with UK treatment. People travelled to 13 different countries, the most popular being Spain and the Czech Republic. Most organized their own treatment and travel. The mean age of women seeking treatment was 38.8 years (range 29–46 years) and the multiple pregnancy rate was 19%.

CONCLUSIONS

UK residents have diverse reasons for, and approaches to, seeking overseas treatment and do not conform to media stereotypes. Further research is needed to explore implications of cross-border treatment for donors, offspring and healthcare systems.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

The objective of this study was to investigate the views of patients and experts in Germany on information provision and decision-making in assisted reproduction treatment (ART).

METHODS

Standard questionnaire techniques were used for interviewing Reproductive Physicians (n= 230), Psychosocial Counsellors (n = 66) and Patients (n = 1590). Descriptive data analyses and non-parametric tests for significance were performed.

RESULTS

Higher scores were assigned for information on the chances for treatment success and on direct, physical risks of fertility treatment than for information on the risks and burden of multiple pregnancies and on the emotional risks and burden associated with infertility treatment. Three-quarters (74%) of the Patients (P) reported that they had experienced an overwhelming desire for a child at some point during their treatment, and half (47%) stated that they had experienced the feeling of losing control over the situation. According to 25% of the Reproductive Physicians (RP) and 47% of the Psychosocial Counsellors (PC), patients are often or very often limited in their capacity to decide when to stop the treatment.

CONCLUSIONS

A significant number of patients in reproductive care in Germany are not well informed on all the aspects that are relevant for treatment decision-making, are overwhelmed by their desire for a child, lose control over the situation, and are limited in their capacity to end unsuccessful treatment. Information provision should be ensured and monitored during treatment by standardized safeguards. A strategy for stopping ART and embarking on alternative ways of coping with infertility should be installed from the outset of every treatment.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

A possible and neglected concern in women with endometriosis undergoing IVF is the potential risk of progression of the disease. We set up a prospective study mainly aimed at evaluating the impact of IVF on endometriosis-related symptoms.

MATERIALS AND METHODS

Women with surgical or echographic diagnosis of endometriosis and selected for IVF were included. In the month preceding the IVF attempt and at a second evaluation 3–6 months after the cycle, women who did not get pregnant underwent clinical assessment and transvaginal ultrasonography. Each patient was requested to complete a questionnaire on the presence, severity and modifications of endometriosis-related symptoms before and after the IVF cycle.

RESULTS

Overall, 64 patients completed the study protocol. The Biberoglu–Behrman Scores and the Verbal Rate Scales for dysmenorrhea, dispareunia and chronic pelvic pain did not worsen after the procedure. Other endometriosis-related symptoms also did not change. There was no modification in size and number of endometriomas and deep peritoneal nodules. The number (%) of women reporting general improvement and worsening were 14 (22%) and 7 (11%), respectively.

CONCLUSIONS

IVF does not expose women to a consistent risk of endometriosis-related symptoms progression.

Source:
http://humrep.oxfordjournals.org/rss/current.xml