Gene pathway analysis of the endometrium at the start of the window of implantation in women with unexplained infertility and unexplained recurrent pregnancy loss: is unexplained recurrent pregnancy loss a subset of unexplained infertility?

This study aims to understand differences/similarities in the genetic profile of the endometrium at the start of window of implantation (WOI) in women with unexplained infertility (UI) and unexplained recurrent pregnancy loss (uRPL). Differentially expressed genes (DEGs) from the endometrium were evaluated using gene expression array and pathway enrichment analysis was performed to analyse gene expression pathways involved in both conditions. We found 2,171 genes arranged in 117 pathways and 730 genes arranged in 33 pathways differentially expressed in endometrium of patients in UI and uRPL, respectively. Complement-coagulation cascades, morphine addiction pathway, and PI3K-Akt signalling pathway were predominantly differentially expressed in UI. Cancer pathways, NF-κB signalling pathway, and actin cytoskeleton regulation pathway showed significant changes in uRPL. Forty-eight percent of DEGs and 84% of differentially expressed pathways in uRPL were found in the endometrium of UI patients. Unexpected close association in gene expression pathways between UI and uRPL is observed supporting the hypothesis 'uRPL is a clinical subset of UI'. Yet 100% DEGs overlap wasn't found suggesting the endometrium has still some different gene expression patterns at start of WOI in UI and uRPL. Lastly, diagnostic tools may be developed for uRPL because more specific genes-pathways are involved compared with UI, which shows broader genetic expression profile.

Impact of endometrial thickness change in response to progesterone on live birth rates embryo transfers with fresh oocyte donation cycles.

Endometrial thickness (ENT) measurements are important to evaluate endometrial receptivity. The effect of endometrial thickness on pregnancy outcomes has been discussed for many years with conflicting results. The aim of our study was to find out the effect of endometrial thickness (ENT) change in response to progesterone on pregnancy outcomes in embryo transfer (ET) of fresh oocyte donation (OD) recipients. The study was designed retrospectively including 134 embryo transfers with fresh OD recipients. ENT was measured by ultrasonography (USG) on the day of initial progesterone administration (ENT1) and on ET day (ENT2). The primary outcome was to determine any correlation between the ENT change and pregnancy outcomes. ENT increased in 56.7% of cases and decreased in 43.4%. Clinical pregnancy rate (CPR) in recipients with increased ENT was 76.3%, and live birth rate (LBR) was 72.4%. CPR in recipients with decreased ENT was 69.0% and LBR was 65.5%. There was no significant difference between recipients with either increased or decreased ENT regarding CPR and LBR (p = .225 and p = .253, respectively). Our study revealed that ENT change after 6 days of progesterone administration, whether increased or decreased, does not have any significant effect on LBR and CPR in fresh OD recipients.IMPACT STATEMENTWhat is already known on this subject? Measurement of endometrial thickness is beneficial to determine the endometrial receptivity. However, there is controversy in the literature regarding the usefulness of measuring endometrial thickness.What do the results of this study add? To the best of our knowledge, this is the first study performed with fresh oocyte donation cycles with large number of recipients for live birth rate outcomes in the literature so far. In this study, we sought to assess the impact of endometrial thickness change, in response to 6 days of progesterone administration, on live birth rate and clinical pregnancy rate in embryo transfer of fresh oocyte donation recipients. We did not find no significant effect of endometrial thickness change on live birth rate when fresh young donor oocytes are fertilised with sperms having normal parameters, and implanted in oestrogen and progesterone primed endometrium.What are the implications of these findings for clinical practice and/or further research? Measurement of endometrial thickness in patients under infertility treatment provides little benefit to clinical outcomes.

Impact of establishing a specialized hepatobiliary unit on liver resections in a non-specialized tertiary centre in regional Australia.

BACKGROUND: In April 2018, a dedicated hepatobiliary unit was established in a tertiary hospital in North Queensland. Changes included the employment of a hepatobiliary-trained surgeon, centralized referrals, and formalized multidisciplinary team meetings. This study aimed to evaluate the impact of establishing a hepatobiliary unit on outcomes after liver resection, in a regional centre where such procedures were previously performed by non-specialist general surgeons. METHODS: Adult patients who underwent elective liver resection in Townsville from 2013 to 2020 were included in the study. Outcomes after liver resection were collected across two study periods - before and after the hepatobiliary unit was established. The primary end points were a before and after comparison of the 90-day morbidity and mortality and the R1 margin rates. RESULTS: Across the two study periods, 76 and 77 patients, respectively, underwent liver resection. Rates of R1 resection, 90-day mortality and major complications were not significantly different between the two study periods. Primary tumours (14.5% before versus 50.6% after) and cirrhosis (1.3% before versus 14.3% after) were significantly higher in the latter period, as was the median length of stay (4 days before versus 6 days after). Annual surgical volume increased by 75% in the period after 2018 compared to the 5 years preceding it. CONCLUSION: Establishing a centralized hepatobiliary unit in a tertiary regional centre resulted in increased surgical volume and case complexity, with no change in early outcomes after liver resection. Overall, this dedicated unit improved the accessibility of a subspecialty surgical service in regional Australia.

Onco-fertility and personalized testing for potential for loss of ovarian reserve in patients undergoing chemotherapy: proposed next steps for development of genetic testing to predict changes in ovarian reserve.

Women of reproductive age undergoing chemotherapy face the risk of irreversible ovarian insufficiency. Current methods of ovarian reserve testing do not accurately predict future reproductive potential for patients undergoing chemotherapy. Genetic markers that more accurately predict the reproductive potential of each patient undergoing chemotherapy would be critical tools that would be useful for evidence-based fertility preservation counselling. To assess the possible approaches to take to develop personalized genetic testing for these patients, we review current literature regarding mechanisms of ovarian damage due to chemotherapy and genetic variants associated with both the damage mechanisms and primary ovarian insufficiency. The medical literature point to a number of genetic variants associated with mechanisms of ovarian damage and primary ovarian insufficiency. Those variants that appear at a higher frequency, with known pathways, may be considered as potential genetic markers for predictive ovarian reserve testing. We propose developing personalized testing of the potential for loss of ovarian function for patients with cancer, prior to chemotherapy treatment. There are advantages of using genetic markers complementary to the current ovarian reserve markers of AMH, antral follicle count and day 3 FSH as predictors of preservation of fertility after chemotherapy. Genetic markers will help identify upstream pathways leading to high risk of ovarian failure not detected by present clinical markers. Their predictive value is mechanism-based and will encourage research towards understanding the multiple pathways contributing to ovarian failure after chemotherapy.

Luteinizing Hormone Action in Human Oocyte Maturation and Quality: Signaling Pathways, Regulation, and Clinical Impact.

The ovarian follicle luteinizing hormone (LH) signaling molecules that regulate oocyte meiotic maturation have recently been identified. The LH signal reduces preovulatory follicle cyclic nucleotide levels which releases oocytes from the first meiotic arrest. In the ovarian follicle, the LH signal reduces cyclic nucleotide levels via the CNP/NPR2 system, the EGF/EGF receptor network, and follicle/oocyte gap junctions. In the oocyte, reduced cyclic nucleotide levels activate the maturation promoting factor (MPF). The activated MPF induces chromosome segregation and completion of the first and second meiotic divisions. The purpose of this paper is to present an overview of the current understanding of human LH signaling regulation of oocyte meiotic maturation by identifying and integrating the human studies on this topic. We found 89 human studies in the literature that identified 24 LH follicle/oocyte signaling proteins. These studies show that human oocyte meiotic maturation is regulated by the same proteins that regulate animal oocyte meiotic maturation. We also found that these LH signaling pathway molecules regulate human oocyte quality and subsequent embryo quality. Remarkably, in vitro maturation (IVM) prematuration culture (PMC) protocols that manipulate the LH signaling pathway improve human oocyte quality of cultured human oocytes. This knowledge has improved clinical human IVM efficiency which may become a routine alternative ART for some infertile patients.

Comparison of endometrial prostanoid profiles in three infertile subgroups: the missing part of receptivity?

OBJECTIVE: To study the prostanoid profile of the endometria of patients with recurrent implantation failure (RIF), unexplained infertility (UIF), and recurrent miscarriages (RM), and to compare them with the endometria of healthy fertile controls. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENT(S): Fifteen patients with RIF, 18 patients with UIF, 16 patients with RM, and 23 fertile controls were recruited. INTERVENTION(S): Endometrial samples were taken during the window of implantation. After tissue homogenization and extraction, analysis with ultra-performance liquid chromatography diode array detector electrospray ionisation tandem mass spectrometry was performed. MAIN OUTCOME MEASURES: Concentrations of prostaglandin (PG) D1, PGE1, PGF1α, 6-ketoPGF1α, PGD2, PGE2, PGF2α, 15-deoxy-Δ12,14-PGJ2, PGD3, PGE3, PGF3α, thromboxane B2, 13,14-dihydro-PGE1, 13,14-dihydro-PGF1α, 13,14-dihydro-PGF2α, 13,14-dihydro-15-keto-PGE1, 13,14-dihydro-15-keto-PGE2, and 13,14-dihydro-15-keto-PGF2α were assessed. RESULT(S): Comparison of the endometria of patients with UIF and the controls showed no statistically significant differences. When the endometria of patients with RIF were compared with the controls, thromboxane B2 (TXB2) was found significantly higher (843.1 pg/mg vs. 133.5 pg/mg). When the endometria of patients with RM were compared with controls, 13,14-dihydro-15-keto PGF2α and TXB2 were found significantly higher (3907.30 pg/mg vs. 17.80 pg/mg and 858.7 pg/mg vs. 133.5 pg/mg respectively). CONCLUSION(S): We identified increased endometrial presence of TXB2 in patients with RM and RIF, and 13,14-dihydro-15-keto PGF2α in patients with RM. Although common ground is observed for RM and RIF, prostanoids, on the other hand, might make their own contribution to endometrial receptivity as important as genes and proteins. Attempts to normalize the prostaglandin profile of the endometrium via enzymatic activity can open new therapeutic options.

Potential Marker Pathways in the Endometrium That May Cause Recurrent Implantation Failure.

The aim of this prospective cohort study was to identify altered biologic processes in the endometrium that may be potential markers of receptive endometrium in patients with repeated implantation failure (RIF) as compared with fertile controls. The study was conducted in a university-affiliated in vitro fertilization (IVF) gynecology clinic and molecular biology and genetics laboratory. Healthy fertile controls (n = 24) and patients with RIF (n = 24) were recruited. Window of implantation gene profiling associated with RIF was performed. Six hundred forty-one differentially expressed genes were identified, and 44 pathways were found enriched. Upon clustering of the enriched pathways, 9 representative pathways were established. The important pathways that were identified included circadian rhythm, pathways in cancer, proteasome, complement and coagulation cascades, citrate cycle, adherens junction, immune system and inflammation, cell cycle, and renin-angiotensin system. The involvement of the circadian rhythm pathway and other related pathways may alter the endometrium's functioning to ultimately cause RIF. Furthermore, we found that the pathogenesis of RIF was multifaceted and that numerous processes were involved. We believe that a better understanding of the underlying mechanisms of RIF will ultimately give rise to better treatment opportunities and to better outcomes in IVF.

Effects of Irisin and Exercise on Metabolic Parameters and Reproductive Hormone Levels in High-Fat Diet-Induced Obese Female Mice.

It has been documented that exogenously administered irisin (1010 fibronectin-type III domain-containing 5 [FNDC5]), which is a new polypeptide hormone, induces the browning of subcutaneous fat and thermogenesis. In this study, effects of physical activity and exogenous administration of irisin were investigated on parameters related with reproduction and metabolism in the high-fat diet-induced obesity model of the female C57BL/6J mice. Sixty mice were gathered at age approximately 5 to 6weeks and were divided into 3 groups. Control group remained sedentary. Irisin group remained also sedentary but intravenously received 1010 FNDC5-expressing adenovirus after 20 weeks. Exercise group performed treadmill after 6 weeks. All mice were sacrificed 22 to 23 weeks after the start of the study. There was a significantly greater Δ weight in the controls compared with the irisin and exercise groups ( P < .05). Glucose and insulin levels were significantly higher in the controls ( P < .05). The serum irisin level was significantly higher in the exercise group ( P < .05). Serum luteinizing hormone levels were significantly increased in the irisin group ( P < .05). Serum anti-Müllerian hormone levels were significantly higher in irisin and exercise groups ( P < .05). There were significant negative correlations between serum irisin levels and Δ weight and homeostatic model assessment of insulin resistance ( r = -0.327, r = -0.297, respectively; P < .05 for both). The numbers of primordial follicles per ovary were similar ( P > .05), whereas primary and secondary follicles per ovary were higher in the irisin and exercise groups compared with controls ( P < .05). Pharmacologic introduction of irisin may improve metabolic factors such as insulin sensitivity and obesity by promoting weight loss and consequently improving the reproductive potential.

Intraneural Injection of ATP Stimulates Regeneration of Primary Sensory Axons in the Spinal Cord.

Injury to the peripheral axons of sensory neurons strongly enhances the regeneration of their central axons in the spinal cord. It remains unclear on what molecules that initiate such conditioning effect. Because ATP is released extracellularly by nerve and other tissue injury, we hypothesize that injection of ATP into a peripheral nerve might mimic the stimulatory effect of nerve injury on the regenerative state of the primary sensory neurons. We found that a single injection of 6 µl of 150 µm ATP into female rat sciatic nerve quadrupled the number of axons growing into a lesion epicenter in spinal cord after a concomitant dorsal column transection. A second boost ATP injection 1 week after the first one markedly reinforced the stimulatory effect of a single injection. Single ATP injection increased expression of phospho-STAT3 and GAP43, two markers of regenerative activity, in sensory neurons. Double ATP injections sustained the activation of phospho-STAT3 and GAP43, which may account for the marked axonal growth across the lesion epicenter. Similar studies performed on P2X7 or P2Y2 receptor knock-out mice indicate P2Y2 receptors are involved in the activation of STAT3 after ATP injection or conditioning lesion, whereas P2X7 receptors are not. Injection of ATP at 150 µm caused little Wallerian degeneration and behavioral tests showed no significant long-term adverse effects on sciatic nerve functions. The results in this study reveal possible mechanisms underlying the stimulation of regenerative programs and suggest a practical strategy for stimulating axonal regeneration following spinal cord injury.SIGNIFICANCE STATEMENT Injury of peripheral axons of sensory neurons has been known to strongly enhance the regeneration of their central axons in the spinal cord. In this study, we found that injection of ATP into a peripheral nerve can mimic the effect of peripheral nerve injury and significantly increase the number of sensory axons growing across lesion epicenter in the spinal cord. ATP injection increased expression of several markers for regenerative activity in sensory neurons, including phospho-STAT3 and GAP43. ATP injection did not cause significant long-term adverse effects on the functions of the injected nerve. These results may lead to clinically applicable strategies for enhancing neuronal responses that support regeneration of injured axons.

A randomized, single-blind, prospective trial comparing three different gonadotropin doses with or without addition of letrozole during ovulation stimulation in patients with poor ovarian response.

OBJECTIVE: The aim of this randomized controlled trial (RCT) was to investigate whether IVF outcomes would differ between patients with POR who received three different gonadotropin doses with or without the addition of letrozole during ovulation stimulation. STUDY DESIGN: Only those who fulfilled two of the three Bologna criteria were included to the study. 95 patients met the inclusion criteria and agreed to participate in the study. In the first group, 31 patients were treated with 450IU gonadotropins. In the second group, 31 patients were treated with 300IU gonadotropins. The third group comprised 33 patients and was treated with 150IU gonadotropins in combination with letrozole. RESULTS: The results indicate that differences in doses of hMG and rFSH in patients with POR result in a similar number of retrieved MII and fertilized oocytes, similar fertilization rates, number of transferred embryos, implantation, cancelation, chemical, clinical, and ongoing pregnancy rates. CONCLUSIONS: Increasing the dose of gonadotropins during ovulation stimulation is an intuitively appealing approach when the patient is a poor responder. However, increasing the dose does not necessarily improve the reproductive outcome. Using a mild stimulation with addition of letrozole was as effective as stimulation with higher doses of gonadotropins alone in this patient population.

Pain and functional outcomes following vertebroplasty for vertebral compression fractures - A tertiary centre experience.

OBJECTIVES: There is a dearth of comparative outcome data on vertebroplasty for the treatment of vertebral compression fractures (VCF) according to vertebral level, the number of levels and aetiology. The aim of this study was to investigate the improvement of pain and function following vertebroplasty for a heterogeneous cohort of patients with medically refractory VCF. METHODS: A prospective observational study was conducted on a cohort of consecutive patients undergoing vertebroplasty following at least 4 weeks of failed medical management, between April 2007 and March 2012 at a single neurosurgical centre. Pain visual analogue scale (VAS) scores, Oswestry Disability Index (ODI) scores, analgesic usage and complications were recorded preoperatively and at day 1, week 1, 1 month, 6 months and 1 year postoperatively. Intraoperative vertebral body biopsy was performed routinely. RESULTS: Two hundred and two levels were augmented in 147 patients. The most common levels augmented were T12 (17%), L1 (18%) and L4 (10%). Significant reductions in pain VAS and ODI scores were evident at day 1 and sustained at up to 1 year postoperatively (p < 0.001). They were not dependent on the level of fracture (T3-10, T11-L2 and L3-S1) (p > 0.05), the number of levels treated (single level, two-level and > two level) (p > 0.05) or aetiology of VCF (p > 0.05). At 1 year postoperatively, 79% (113/142) had no or reduced analgesic usage. The complication rate was 6% (9/147). There were five mortalities, none of which was directly related to surgery. CONCLUSION: Vertebroplasty for medically refractory VCF may offer sustained improvement in pain and function. The procedure is associated with low morbidity and mortality.

Role of Mucin 1 and Glycodelin A in recurrent implantation failure.

OBJECTIVE: To evaluate and compare the levels of Mucin 1 (MUC-1) and Glycodelin A (GdA) in precisely timed endometrial biopsies and blood samples taken from women with recurrent implantation failure, and women with proven fertility, in a control group. DESIGN: Molecular studies in human blood and tissue. SETTING: University hospital. PATIENT(S): Women with recurrent implantation failure and women with proven fertility. INTERVENTION(S): Primary endometrial cells and blood samples during the implantation "window" (between day 7 and day 9 after the surge in luteinizing hormone). MAIN OUTCOME MEASURE(S): Expression of MUC-1 and GdA in the human endometrium and in blood during the implantation window were analyzed by enzyme-linked immunosorbent assay. Additionally, MUC-1 and GdA levels in tissue were analyzed by western blot during the same period. RESULT(S): Both blood and tissue measurements of MUC-1 and GdA were significantly lower in women with recurrent implantation failure than in fertile women during the implantation window. In addition, we found a highly significant correlation between blood vs. tissue measurements of both MUC-1 and GdA. CONCLUSION(S): The present study reveals that blood and tissue levels of MUC-1 and GdA are much lower in women with RIF, compared with those in fertile women. Receptivity can be evaluated with noninvasive blood sampling, rather than more-invasive endometrium sampling, as the blood and tissue measurements of MUC-1 and GdA are correlated.

Utility of routine biopsy at vertebroplasty in the management of vertebral compression fractures: a tertiary center experience.

OBJECT: The authors assess the utility of routine biopsy at vertebroplasty for vertebral compression fracture (VCF) as a tool in the early detection of malignancy in presumed benign VCF. METHODS: A prospective observational study was conducted on a cohort of consecutive patients undergoing vertebroplasty over a 5-year period between April 2006 and March 2011 at the Royal London Hospital. Polymethylmethacrylate cement injection was used in every procedure. Intraoperative vertebral body biopsy was performed routinely at every level of VCF. Pain visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores, analgesic usage, and complications were recorded preoperatively and at 1 day, 1 week, 1 month, 6 months, and 1 year postoperatively. RESULTS: A total of 202 levels were augmented in 147 patients. The most common levels augmented were T-12 (17%), L-1 (18%), and L-4 (10%). Analysis of 184 routine vertebral biopsies in 135 patients revealed that in 86 patients with presumed osteoporosis and no prior cancer diagnosis, 4 (4.7%) had a malignant VCF. In 20 known cancer patients presumed to be in remission, 2 (10%) had a malignant VCF. Routine vertebral biopsy returned an overall cancer diagnosis rate of 5.5% (6 of 109) when combining the 2 groups (patients with no prior history of cancer or cancer thought to be in remission). In these 6 patients, history, examination, laboratory tests, and preprocedure imaging all failed to suggest malignancy diagnosed at routine biopsy. Significant reductions in pain VAS and ODI scores were evident at Day 1 and were sustained at up to 1 year postoperatively (p < 0.001). They were not dependent on the level of fracture (T3-10, T11-L2, or L3-S1) (p > 0.05), number of levels treated (single level, 2 levels, or > 2 levels) (p > 0.05), or etiology of VCF (p > 0.05). The complication rate was 6% (9 of 147). There were 5 deaths, none of which were directly related to surgery. CONCLUSIONS: Routine vertebral biopsy performed at vertebroplasty may demonstrate cancer-related VCFs in unsuspected patients with no previous cancer diagnosis or active malignancy in patients previously thought to be in remission. This early diagnosis of cancer or relapsed disease will play an important role in expediting patients' subsequent cancer management. In cases of multiple-level VCF, the authors advocate biopsy at each level to maximize the diagnostic yield from the specimens and to avoid missing a malignancy at a single level.

Lentiviral mediated expression of a NGF-soluble Nogo receptor 1 fusion protein promotes axonal regeneration.

Nogo receptor 1 (NgR1) mediates the inhibitory effects of several myelin-associated inhibitors (MAIs) on axonal regeneration in the central nervous system. A truncated soluble NgR1 (sNgR) has been reported to act as a decoy receptor to block the actions of MAIs. In this study, we fused the sNgR to nerve growth factor (NGF) and used NGF as a carrier to deliver sNgR to the intercellular space to neutralize MAIs. NGF in NGF-sNgR remained biologically active and induced sprouting of calcitonin gene related peptide containing axons when expressed in the spinal cord using a lentiviral vector (LV). Secreted NGF-sNgR promoted neurite outgrowth of dissociated dorsal root ganglion neurons on myelin protein substrate. In a rat dorsal column transection model, regenerating sensory axons were found to grow into the lesion cavity in animals injected with LV/NGF-sNgR, while in animals injected with LV/GFP or LV/NGF-GFP few sensory axons entered the lesion cavity. The results indicate that NGF-sNgR fusion protein can reduce the inhibition of MAIs and facilitate sensory axon regeneration. The fusion constructs may be modified to target other molecules to promote axonal regeneration and the concept may also be adapted to develop gene therapy strategies to treat other disorders.

The relationship between copper, homocysteine and early vascular disease in lean women with polycystic ovary syndrome.

This study investigates copper (Cu) levels and vascular dysfunction in lean women with polycystic ovary syndrome (PCOS). 44 subjects with PCOS, diagnosed according to Rotterdam criteria, and 42 healthy subjects matched for body mass index and age. Comparison of serum Cu, homocysteine, carotid intima-media thickness (CIMT), brachial artery flow mediated dilation (FMD) was carried out between PCOS patients and the control group. Clinical study was done in Namik Kemal University School of Medicine. The CIMT and concentration of Cu in PCOS patients was significantly higher than the healthy controls. FMD levels in PCOS patients were significantly lower than those in controls. In PCOS patients, CIMT was correlated with estrogen and Cu levels. However, FMD was correlated with age and Cu levels. Among these contributing factors, Cu levels were correlated with a change in CIMT and FMD. CIMT and FMD in PCOS patients were related to Cu levels as well as several cardiovascular risk factors. Thus, increased Cu levels may be responsible for the increased risk of early vascular disease in women with PCOS.

Müllerianosis: four developmental (embryonic) mullerian diseases.

The theory of müllerianosis predicts that embryonic müllerian tissue, misplaced during organogenesis, results in the formation of 4 benign müllerian diseases-developmental adenomyosis, endometriosis, endosalpingiosis, and endocervicosis-(developmental müllerian diseases) that will be identified in human female fetuses, infants, children, adolescents, and adults. Direct evidence is presented to support the existence of developmental adenomyosis, developmental endometriosis, and developmental endocervicosis in human female fetuses along with strong circumstantial evidence supporting the existence of all 4 developmental müllerian diseases in human female infants, children, adolescents, and adults. This evidence throws light upon the pathogenesis of rare müllerian lesions whose pathogenesis remains inexplicable by classical and modern theories. Furthermore, this research has scientific and clinical relevance: scientific relevance because it opens up a new field of comparative research-the 4 developmental müllerian diseases complement the 4 acquired müllerian diseases; clinical relevance because it identifies rare müllerian diseases curable by complete surgical excision.

Postpartum depression in special populations: a review.

UNLABELLED: This review article aims to define and characterize postpartum depression; to discuss the social, financial, regulatory and legal implications of the disorder; and to elucidate its impact on special groups, namely adolescents, immigrants, fathers, and those of different racial and ethnic groups. A MEDLINE review of the current literature was run on postpartum depression, using the key words postpartum depression, depression, pregnancy, peripartum, or postpartum, from the years 2000 to 2011. Postpartum depressive syndromes place women and their children at risk of suicide and infanticide if not appropriately diagnosed and treated. Screening should occur within 4 to 6 weeks postpartum. Women with a history of depression before or during pregnancy, adolescents, those with low incomes and poor social support, or with a history of substance abuse, are especially at high risk. Treatments include antidepressants and psychotherapy. The unique populations of adolescents, fathers, immigrants, and certain racial and ethnic groups require special consideration in terms of diagnosis, screening modalities, and treatment. Collaboration between obstetrical providers and behavioral health professionals can ensure improved outcomes. It was found that postpartum depression is a challenging diagnosis and may be difficult to treat. A multidisciplinary approach is warranted to prevent life-threatening consequences in mothers and their children. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After participating in this activity, physicians should be better able to diagnose postpartum depression and to analyze the social, financial, regulatory and legal implications of the disorder; and to evaluate its impact on special groups, namely adolescents, immigrants, fathers, and those of different racial and ethnic groups.

Risk for advanced-stage endometrial cancer in surgical specimens from patients with complex endometrial hyperplasia with atypia.

OBJECTIVES: To determine the incidence of endometrial cancer in patients undergoing hysterectomy for atypical complex endometrial hyperplasia and to study the risk of advanced endometrial cancer that may be associated with extra-uterine disease. METHODS: A retrospective chart review was performed of the records of all women who underwent hysterectomy for a preoperative diagnosis of complex hyperplasia with atypia from two teaching hospitals between 1999 and 2006. Demographic and clinical variables were collected and analyzed for the 80 patients identified by the initial screening methods. RESULTS: After screening and exclusions, 66 women with a preoperative diagnosis of atypical complex hyperplasia who subsequently underwent a hysterectomy were identified. Eleven of the 66 patients with atypical complex hyperplasia had a diagnosis of endometrial carcinoma in the hysterectomy specimens (17%). No endometrial cancer patient was staged greater than stage 1B or had greater than grade 2 disease. The patients with endometrial cancer were older (p < 0.05). Evidence of myometrial invasion was found in 63% (7/11) of the cancer cases, but all were less than 50% of the myometrium. CONCLUSION: Endometrial cancer found at the time of hysterectomy for complex hyperplasia with atypia may be associated with less advanced disease.

Promoting survival, migration, and integration of transplanted Schwann cells by over-expressing polysialic acid.

The poor survival and migration of transplanted Schwann cells (SCs) are major drawbacks for their clinical application in cell therapy for neurotrauma. To overcome such drawbacks we genetically modified SCs to over-express polysialic acid (PSA) by lentiviral delivery of polysialyltransferase (PST) to study whether over-expression of PSA could enhance their survival, migration, and integration when transplanted into the spinal cord. It was found that more PSA-expressing SCs (PST/SCs) survived than GFP-expressing SCs (GFP/SCs) after transplantation, although cell loss was still quite significant. PSA expression did not enhance the motility of transplanted SCs in uninjured spinal cord. However, in a spinal cord crush injury model PST/SCs transplanted caudal to the lesion showed that increased number of PST/SCs migrated to the injury site compared with that of GFP/SCs. Induced expression of PSA in spinal cord can further facilitate the infiltration of PST/SCs into the lesion site. PST/SCs were also shown to intermingle well with host spinal cells while GFP/SCs formed boundaries with host tissue. This was confirmed by an in vitro confrontation assay showing that more PST/SCs crossed over to astrocyte territory than GFP/SCs. Furthermore, PST/SCs induced much less expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycan in the surrounding tissues than GFP/SCs, indicating that expression of PSA on SCs do not cause significant stress response of astrocytes. These results demonstrate that expression of PSA on SCs significantly changes their biological properties and makes them more feasible for neural repair after neurotrauma.