Peri-implantation glucocorticoid administration for assisted reproductive technology cycles.

BACKGROUND: The use of peri-implantation glucocorticoids has been advocated to improve embryo implantation during assistive reproductive technology (ART) cycles such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). It has been proposed that glucocorticoids may improve the intrauterine environment by acting as immunomodulators to reduce the uterine natural killer (NK) cell count and activity, normalising the cytokine expression profile in the endometrium and by suppression of endometrial inflammation. OBJECTIVES: To evaluate the effectiveness and safety of glucocorticoids versus no glucocorticoids administered around the time of anticipated implantation in women undergoing IVF or ICSI. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group specialised register, CENTRAL (now also containing output from two trial registers and CINAHL), MEDLINE and Embase, on 20 December 2021, together with reference checking, contact with experts in the field and relevant conference proceedings to identify additional studies. This review is an update of the review first published in  2007 and last updated in 2012. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the efficacy of supplementary systemic administration of glucocorticoids in the peri-implantation period with a placebo or no glucocorticoids in subfertile women undergoing IVF or ICSI were included. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcomes were live birth rate and multiple pregnancy. MAIN RESULTS: We included 16 RCTs (2232 couples analysed). We are uncertain whether glucocorticoids improved live birth rates (odds ratio (OR) 1.37, 95% confidence interval (CI) 0.69 to 2.71; 2 RCTs, n = 366; I2 = 7%; very low-certainty evidence). This suggests that if the chance of live birth following no glucocorticoids/placebo is assumed to be 9%, the chance following glucocorticoids would be between 6% and 21%. We are also uncertain whether there was a difference between peri-implantation glucocorticoids on multiple pregnancy rates per couple (OR 0.86, 95% CI 0.33 to 2.20; 4 RCTs, n = 504; I2 = 53%; very low-certainty evidence). The I2 of 53% may represent moderate statistical heterogeneity and results have to be interpreted with caution. With regard to pregnancy rates, we are uncertain whether there was a difference between ongoing pregnancy rates after glucocorticoids versus no glucocorticoids/placebo (OR 1.19, 95% CI 0.80 to 1.76; 3 RCTs, n = 476; I2 = 0%; very low-certainty evidence) and clinical pregnancy rates after glucocorticoids versus no glucocorticoids/placebo (OR 1.17, 95% CI 0.95 to 1.44; 13 RCTs, n = 1967; I2 = 0%; low-certainty evidence). This suggests that if the chance of clinical pregnancy following no glucocorticoids/placebo is assumed to be 25%, the chance following glucocorticoids would be between 24% and 32%. Furthermore, we are also uncertain whether peri-implantation glucocorticoids influenced miscarriage rates per couple (OR 1.09, 95% CI 0.63 to 1.87; 6 RCTs, n = 821; I2 = 0%; very low-certainty evidence), the incidence of ectopic pregnancies per couple (OR 2.28, 95% CI 0.33 to 15.62; 3 RCTs, n = 320; I2 = 0%; very low-certainty evidence) and ovarian hyperstimulation syndrome (OHSS) per couple (OR 1.07, 95% CI 0.60 to 1.90; 3 RCTs, n = 370; I2 = 0%; very low-certainty evidence) compared to no glucocorticoids/placebo. The evidence was very low to low certainty: the main limitations were serious risk of bias due to poor reporting of study methods, and serious imprecision. AUTHORS' CONCLUSIONS: Overall, there was insufficient evidence that administration of peri-implantation glucocorticoids in IVF/ICSI cycles influenced clinical outcomes. These findings were limited to the routine use of glucocorticoids in subfertile women undergoing IVF or ICSI.

Intralipid infusion at time of embryo transfer in women with history of recurrent implantation failure: A systematic review and meta-analysis.

AIM: Recurrent implantation failure (RIF) affects 10% of couples undergoing assisted conception, often due to poor endometrial receptivity. We conducted a systematic review and meta-analysis to evaluate the effectiveness of Intra-venous intralipid (IVI) in improving pregnancy rates in women with history of RIF using. METHODS: We searched MEDLINE, EMBASE, and CENTRAL for any randomized trials evaluating the use of IVI at the time of embryo transfer in women undergoing assisted conception until September 2020. We extracted data in duplicate and assessed risk of bias using the Cochrane Risk of Bias tools. We meta-analyzed data using a random effect model. RESULTS: We included five randomized trials reporting on 843 women with an overall moderate risk of bias. All trials used 20% IVI solution at the time of embryo transfer compared to normal saline infusion or no intervention (routine care). The IVI group had a higher chance of clinical pregnancy (172 vs 119, risk ratio [RR] 1.55, 95% confidence interval [CI] 1.16-2.07, I2 44.2%) and live birth (132 vs 73, RR 1.83, 95% CI 1.42-2.35, I2 0%) post treatment compared to no intervention. Our findings are limited by the small sample size and the variations in treatment protocols and population characteristics. CONCLUSION: There is limited evidence to support the use of IVI at the time of embryo transfer in women with the history of RIF. More research is needed before adopting it in clinical practice.

Glucocorticoid supplementation during ovarian stimulation for IVF or ICSI.

BACKGROUND: Ovarian response to stimulation during in-vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) plays an important role in determining live birth rates. Adjuvant treatments during ovarian stimulation that have different modes of action have been used to improve ovarian response to stimulation and outcome of IVF. Glucocorticoids (GCs) are a class of steroid hormones that have been used either alone or in combination with other stimulatory regimens in order to improve folliculogenesis and pregnancy rates. However, considerable uncertainty remains over whether administration of glucocorticoid during ovarian stimulation until oocyte recovery is superior to no glucocorticoid in improving live birth rates in women undergoing IVF/ICSI. OBJECTIVES: To determine the safety and effectiveness of systemic glucocorticoids during ovarian stimulation for IVF and ICSI cycles. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Studies Online (CRSO), MEDLINE, Embase, CINAHL and PsycINFO from inception to 10 October 2016. We handsearched reference lists of articles, trial registers and relevant conference proceedings and contacted researchers in the field. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing adjuvant treatment with systemic glucocorticoids during ovarian stimulation for IVF or ICSI cycles versus no adjuvant treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted the data. Our primary outcome was live birth. Secondary outcomes included clinical pregnancy, multiple pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS) and side-effects. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) and pooled the data using a fixed-effect model. The quality of the evidence was assessed using GRADE methods. MAIN RESULTS: Four RCTs were included in the review (416 women). The trials compared glucocorticoid supplementation during IVF stimulation versus placebo. Two of the studies had data in a form that we could not enter into analysis, so results include data from only two trials (310) women. For the outcome of live birth, data were available for only 212 women, as the larger study had data available from only one study centre.One of the studies gave inadequate description of randomisation methods, but the other was at low risk of bias in all domains. The evidence was rated as low or very low quality for all outcomes, mainly due to imprecision, with low sample sizes and few events.There was insufficient evidence to determine whether there was any difference between the groups in live birth rate (OR 1.08, 95% CI 0.45 to 2.58; 2 RCTs, n = 212, I2 = 0%, low-quality evidence). Our findings suggest that if the chance of live birth with placebo is assumed to be 15%, the chance following supplementation would be between 7% and 31%. There was no conclusive evidence of a difference in the clinical pregnancy rate (OR 1.69, 95% CI 0.98 to 2.90; 2 RCTs, n = 310, I2 = 0%, low-quality evidence).The evidence suggests that if the chance of clinical pregnancy with placebo is assumed to be 24%, the chance following treatment with glucocorticoid supplementation would be between 23% and 47%. There was also insufficient evidence to determine whether there was any difference between the groups in multiple-pregnancy rate (OR 3.32 , 95% CI 0.12 to 91.60; 1 RCT , n = 20, very low-quality evidence) or miscarriage rate (OR 1.00, 95% CI 0.05 to 18.57; 1 RCT, n = 20, very low-quality evidence). Neither of the studies reported OHSS or side-effects. AUTHORS' CONCLUSIONS: The safety and effectiveness of glucocorticoid administration in women undergoing controlled ovarian hyperstimulation for IVF/ICSI cycles (until the day of oocyte retrieval) is unclear due to the small number of studies and low event rates. Whilst glucocorticoids possible increase the clinical pregnancy rate, there may be little or no impact on live birth rate. More research is needed.

Fertility preservation, its effectiveness and its impact on disease status in pre-menopausal women with breast cancer: A systematic review and meta-analysis.

INTRODUCTION: Preservation of reproductive function is a key concern for many premenopausal women with breast cancer, given the known gonadotoxic effects of treatments. The present systematic review aimed to investigate the effectiveness and safety of fertility preservation strategies in pre-menopausal women with breast cancer. METHODS: Primary research assessing fertility preservation strategies of any type was identified. Markers of preservation of fertility including return of menstrual function, clinical pregnancy rates and live birth rates were selected as main outcome measures. An additional analysis of safety data was also performed. RESULTS: Fertility preservation interventions were overall associated with higher fertility outcomes: with a pooled odds ratio 4.14 (95% CI 3.59-4.77) for any kind of fertility preservation intervention. This was seen both for return of menstruation and for clinical pregnancy rate, but not for live birth rates. Fertility preservation was associated with a reduced rate of disease recurrence (OR 0.63 (95% CI 0.49-0.81)), while there was no significant difference in disease free survival (OR 0.88 (95% CI 0.74-1.05)) or in overall survival (OR 0.9 (95% CI 0.74-1.10)) between the fertility preservation group and those who had not undergone fertility preservation. CONCLUSION: Fertility preservation is both effective in preserving reproductive function, and safe with regard to disease recurrence, disease free survival and overall survival in premenopausal women with breast cancer.

Peri-implantation glucocorticoid administration for assisted reproductive technology cycles.

BACKGROUND: In order to improve embryo implantation for in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles the use of glucocorticoids has been advocated. It has been proposed that glucocorticoids may improve the intrauterine environment by acting as immunomodulators to reduce the uterine natural killer (NK) cell count and normalise the cytokine expression profile in the endometrium and by suppression of endometrial inflammation. OBJECTIVES: To investigate whether the administration of glucocorticoids around the time of implantation improved clinical outcomes in subfertile women undergoing IVF or ICSI when compared to no glucocorticoid administration. SEARCH METHODS: The Cochrane Menstrual Disorders and Subfertility Group Trials Register (September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (September 2011), MEDLINE (1966 to September 2011), EMBASE (1976 to September 2011), CINAHL (1982 to September 2011) and Science Direct (1966 to September 2011) were searched. Reference lists of relevant articles and relevant conference proceedings were handsearched. SELECTION CRITERIA: All randomised controlled trials (RCTs) addressing the research question were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and quality of trials and extracted relevant data. MAIN RESULTS: Fourteen studies (involving 1879 couples) were included. Three studies reported live birth rate and these did not identify a significant difference after pooling the (preliminary) results (OR 1.21, 95% CI 0.67 to 2.19). With regard to pregnancy rates, there was also no evidence that glucocorticoids improved clinical outcome (13 RCTs; OR 1.16, 95% CI 0.94 to 1.44). However, a subgroup analysis of 650 women undergoing IVF (6 RCTs) revealed a significantly higher pregnancy rate for women using glucocorticoids (OR 1.50, 95% CI 1.05 to 2.13). There were no significant differences in adverse events, but these were poorly and inconsistently reported. AUTHORS' CONCLUSIONS: Overall, there was no clear evidence that administration of peri-implantation glucocorticoids in ART cycles significantly improved the clinical outcome. The use of glucocorticoids in a subgroup of women undergoing IVF (rather than ICSI) was associated with an improvement in pregnancy rates of borderline statistical significance and should be interpreted with care. These findings were limited to the routine use of glucocorticoids and cannot be extrapolated to women with autoantibodies, unexplained infertility or recurrent implantation failure. Further well designed randomised studies are required to elucidate the possible role of this therapy in well defined patient groups.

Interventions to optimize embryo transfer in women undergoing assisted conception: a comprehensive systematic review and meta-analyses.

BACKGROUND: Several interventions and techniques are suggested to improve the outcome of embryo transfer (ET) in assisted conception. However, there remains no consensus on the optimal practice, with high variations among fertility specialists. OBJECTIVE AND RATIONALE: We conducted a comprehensive systematic review and meta-analyses of randomized controlled trials (RCTs) aiming to identify effective interventions that could be introduced around the time of ET to improve reproductive outcomes. SEARCH METHODS: We searched the electronic databases (MEDLINE, EMBASE and Cochrane CENTRAL) from inception until March 2021 using a multi-stage search strategy of MeSH terms and keywords, and included all RCTs that evaluated an intervention in the 24-h period before/after ET in women undergoing IVF/ICSI. Our primary outcome was clinical pregnancy rate post-ET confirmed as viable pregnancy on ultrasound scan. We assessed the risk of bias in included trials and extracted data in duplicate. We pooled data using a random-effect meta-analysis and reported using risk ratio (RR) with 95% CI. We explored publication bias and effect modifiers using subgroup analyses. OUTCOMES: Our search yielded 3685 citations of which we included 188 RCTs (38 interventions, 59 530 participants) with a median sample size of 200 (range 26-1761). The quality of included RCTs was moderate with most showing a low risk of bias for randomization (118/188, 62.8%) and attrition (105/188, 55.8%) but there was a significant risk of publication bias (Egger's test P = 0.001). Performing ET with ultrasound guidance versus clinical touch (n = 24, RR 1.265, 95% CI 1.151-1.391, I2 = 38.53%), hyaluronic acid versus routine care (n = 9, RR 1.457, 95% CI 1.197-1.261, I2 = 46.48%) and the use of a soft versus hard catheter (n = 27, RR 1.122, 95% CI 1.028-1.224, I2 = 57.66%) led to higher clinical pregnancy rates. Other pharmacological add-ons also showed a beneficial effect including granulocyte colony-stimulating factor (G-CSF: n = 4, RR 1.774, 95% CI 1.252-2.512, I2 = 0), Atosiban (n = 7, RR 1.493, 95% CI 1.184-1.882, I2 = 68.27%) and hCG (n = 17, RR 1.232, 95% CI 1.099-1.382, I2 = 57.76%). Bed rest following ET was associated with a reduction in clinical pregnancy (n = 6, RR 0.857, 95% CI 0.741-0.991, I2 = 0.01%). Other commonly used interventions, such as non-steroidal anti-inflammatory drugs, prophylactic antibiotics, acupuncture and cervical mucus removal, did not show a significant benefit on reproductive outcomes. Our effect estimates for other important outcomes, including miscarriage and live birth, were limited by the varied reporting across included RCTs. WIDER IMPLICATIONS: Using ultrasound guidance, soft catheters and hyaluronic acid at the time of ET appears to increase clinical pregnancy rates. The use of Atosiban, G-CSF and hCG showed a trend towards increased clinical pregnancy rate, but larger trials are required before adopting these interventions in clinical practice. Bed rest post-ET was associated with a reduction in clinical pregnancy and should not be recommended.

Quantitative assessment of pregnancy outcome following recurrent miscarriage clinic care: a prospective cohort study.

OBJECTIVES: To measure pregnancy outcome following attendance at a recurrent miscarriage service and identify factors that influence outcome. DESIGN: Prospective, observational electronic cohort study. SETTING: Participants attending a specialist recurrent miscarriage clinic, with a history of two or more pregnancy losses. 857 new patients attended over a 30-month period and were invited to participate. Participant data were recorded on a bespoke study database, 'Tommy's Net'. PARTICIPANTS: 777 women consented to participate (90.7% of new patients). 639 (82%) women continued within the cohort, and 138 were lost to follow-up. Mean age of active participants was 34 years for women and 37 years for partners, with a mean of 3.5 (1-19) previous pregnancy losses. Rates of obesity (maternal: 23.8%, paternal: 22.4%), smoking (maternal:7.4%, paternal: 19.4%) and alcohol consumption (maternal: 50%, paternal: 79.2%) were high and 55% of participants were not taking folic acid. OUTCOME MEASURES: Biannual collection of pregnancy outcomes, either through prompted self-reporting, or existing hospital systems. RESULTS: 639 (82%) women were followed up. 404 (83.4%) reported conception and 106 (16.6%) reported no pregnancy, at least 6 months following registration. Of those that conceived, 72.8% (294/404) had a viable pregnancy. Maternal smoking and body mass index (BMI) over 30 were significantly higher in those who did not conceive (p=0.001) CONCLUSIONS: Tommy's Net provides a secure electronic repository on data for couples with recurrent pregnancy loss and associated outcomes. The study identified that subfertility, as well as repeated miscarriage, maternal BMI and smoking status, contributed to failure to achieve live birth. Study findings may enable comparison of clinic outcomes and inform the development of a personalised holistic care package.

Early versus delayed urinary catheter removal after hysterectomy: A systematic review and meta-analysis.

OBJECTIVES: In bladder drainage, an essential part of post-hysterectomy care, the optimal timing for removing the urinary catheter is unclear. Our objective was to evaluate the risks and benefits of early (<6 h) vs delayed (>6 h) catheter removal post-hysterectomy. STUDY DESIGN: A systematic review searching MEDLINE, EMBASE and Cochrane CENTRAL from inception till May 2019 for randomised trials of women undergoing hysterectomy. We reported on urinary retention, positive urine culture, urinary tract infection (UTI) (defined by symptoms and/or antibiotic use), post-operative pyrexia, time to ambulation, and length of hospital stay. We assessed risk of bias in included trials and used a random-effect model to generate risk ratios (RR) for dichotomous outcomes and weighted mean differences (WMD) for continuous outcomes, with 95 % confidence intervals (CI). RESULTS: Of 1020 potentially relevant citations, we included 10 randomised trials (1120 women). Four trials had low risk of bias for randomisation and allocation concealment while five had low risk for outcome assessment and selective reporting. Compared to delayed removal, women in the early catheter removal group had a higher risk of urinary retention and needing re-catheterisation (10 RCTs, RR 3.61, 95 %CI 1.21-9.21, I2 = 56 %). There was some reduction in the risk of post-operative UTI (6 RCTs, RR 0.42, 95 %CI 0.18 to 0.96, I2 = 0 %), but we did not find a significant difference in post-operative pyrexia (6 RCTs, RR 0.73, 95 %CI 0.43-1.24, I2 = 18 %) or positive urine cultures (6 RCTs, RR of 0.56, 95 %CI 0.27-1.12, I2 = 55 %). There was no significant difference in the average time to ambulation (3RCTs, WMD -4.6, 95 %CI -9.16 to -0.18, I2 = 98 %) and length of hospital stay (3RCTs, WMD -1.05, 95 %CI -2.42 to 0.31, I2 = 98 %). Our meta-regression on the provision of prophylactic antibiotics did not show a significant effect on the reported outcomes. Our analysis was limited by our inability to adjust for potential effect modifiers such as the surgical route. CONCLUSIONS: Early removal of the urinary catheter <6 h post-hysterectomy seems to increase the risk of urinary retention and needing re-catheterisation, but may reduce post-operative UTI.

Diminished ovarian reserve in recurrent pregnancy loss: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the association between diminished ovarian reserve (DOR) in women at risk of recurrent pregnancy loss (RPL) using ovarian reserve tests. DESIGN: Systematic review and meta-analysis. SETTING: University medical schools. PATIENT(S): Women with a history of RPL. INTERVENTION(S): Systematic reviews of major electronic databases (MEDLINE, EMBASE, Web of Science, and Scopus) for studies that evaluated the incidence of DOR in women with RPL. MAIN OUTCOME MEASURE(S): Association between RPL and DOR. RESULT(S): In studies up to May 2019 we assessed quality using the Newcastle-Ottawa Scale and meta-analyzed data using a random-effect model. We included 15 studies (n = 3,082 women) reporting on six ovarian reserve tests: antimüllerian hormone [AMH], antral follicle count, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and FSH:LH ratio. More women with RPL seemed to have DOR compared with women who did not have RPL as measured by low AMH levels (odds ratio [OR] 2.77; 95% confidence interval [CI], 1.41-5.46) and AFC (OR 2.45; 95% CI, 1.16-5.19). Women with unexplained RPL also seemed to have a higher association with DOR compared with women whose RPL had a known etiology, as measured by low AMH levels (OR 3.23; 95% CI, 1.81-5.76). No statistically significant differences were found in the levels of any of the remaining ovarian reserve tests between those groups of women. CONCLUSION(S): There is an apparent association between DOR and RPL. Low AMH and AFC levels could predict higher odds for pregnancy loss, but more studies are needed to evaluate their prognostic value in the management of women with RPL. SYSTEMATIC REVIEW REGISTRATION NUMBER: Prospero CRD42018114673.

Increased visfatin messenger ribonucleic acid and protein levels in adipose tissue and adipocytes in women with polycystic ovary syndrome: parallel increase in plasma visfatin.

CONTEXT: Polycystic ovary syndrome (PCOS) is a multifaceted metabolic disease linked with insulin resistance (IR) and obesity. Recent studies have shown that plasma levels of the insulin-mimetic adipokine visfatin increase with obesity. Currently, no data exist on the relative expression of visfatin in either plasma or adipose tissue of PCOS women. OBJECTIVES: We investigated the mRNA expression of visfatin from sc and omental (om) adipose tissue and sc adipocytes in women with PCOS compared with matched normal women, as well as visfatin protein in adipose tissue; plasma visfatin was also assessed. DESIGN: Real-time RT-PCR and Western blotting were used to assess the relative mRNA and protein expression of visfatin. Biochemical measurements were performed. RESULTS: There was significant up-regulation of visfatin mRNA in both sc (P < 0.05) and om (P < 0.05) adipose tissue of PCOS women, when compared with normal controls; these findings were also reflected in isolated sc adipocytes (PCOS > controls; P < 0.05). In addition to elevated plasma visfatin levels in women with PCOS (mean +/- sd, 30.2 +/- 10.4 vs. 11.2 +/- 6.2 ng/ml; P < 0.01) when compared with normal controls, visfatin protein levels were significantly greater in both sc and om adipose tissue of PCOS women (P < 0.05 and P < 0.01, respectively). CONCLUSIONS: The precise reason for the up-regulation of visfatin seen in women with PCOS, a proinflammatory state, is unknown. Additional studies are needed to clarify the potential role of visfatin in the pathophysiology of PCOS.

Acquired factor VIII inhibitors as a cause of primary post-partum haemorrhage.

Acquired haemophilia was diagnosed following detailed investigation of a post-partum haemorrhage unresponsive to standard management. Circulating factor VIII inhibitors and low factor VIII levels were detected and intravenous DDAVP treatment lead to a resolution of symptoms. This case highlights the importance of haematological investigations in persisting post-partum haemorrhage.

Homonymous hemianopia following a triplet pregnancy: post-natal cerebral vasculitis or atypical eclampsia.

A 46-year-old woman with a triplet pregnancy developed seizures, an oculogyric crisis and a homonymous hemianopia post-natally. Abnormal neuroimaging studies and lumbar puncture suggested possible cerebral vasculitis. Treatment with aciclovir and prednisolone resulted in a slow resolution of symptoms. This case highlights the difficulty in distinguishing eclampsia from rarer neurological causes of peripartum seizures.

Poor ovarian response to gonadotrophin stimulation the role of adjuvant treatments.

Poor ovarian response to gonadotrophin stimulation represents a clinical problem in in vitro fertilization practice. Women showing poor ovarian response are a heterogeneous group, many of whom have a reduced ovarian reserve and consequently a lower pregnancy potential. Various management strategies have been proposed to improve ovarian response to gonadotrophins, but these have met with limited success. Adjuvant treatments aim to potentiate the effect of exogenous follicle-stimulating hormone. In separate, randomized, placebo-controlled trials low-dose dexamethasone and aspirin have been shown to reduce the incidence of poor response in an initial stimulation cycle. Preliminary studies using pyridostigmine and L-arginine in established poor responders are encouraging but require confirmation in adequately powered studies. Evidence from randomized controlled trials does not support the use of adjuvant growth hormone or growth hormone-releasing hormone in poor responders without overt growth hormone deficiency. The mechanisms of action of adjuvant treatments require further investigation.

Laparoscopic management of interstitial pregnancy with automatic stapler.

A 36-year-old woman was referred by general practitioner to the early pregnancy unit with pelvic pain in her seventh week of pregnancy. She had a transvaginal ultrasound. Unruptured live twin tubal ectopic pregnancy was diagnosed on. Diagnostic laparoscopy revealed an unruptured left interstitial ectopic pregnancy. The interstitial tubal pregnancy was removed by laparoscopic automatic stapler with minimal blood loss. The patient had an uneventful recovery to health.

The anti-atherogenic aspect of metformin treatment in insulin resistant women with the polycystic ovary syndrome: role of the newly established pro-inflammatory adipokine Acute-phase Serum Amyloid A; evidence of an adipose tissue-monocyte axis.

OBJECTIVE: Acute-phase Serum Amyloid A (ASAA) is a novel pro-inflammatory adipokine, increased in obese, insulin resistant subjects. Polycystic ovary syndrome (PCOS) is associated with inflammation and atherosclerosis. We assessed sera, adipose tissue (AT) mRNA and protein levels of ASAA of PCOS women and matched controls. Ex vivo regulation of AT ASAA by d-glucose, effects of metformin treatment on circulating ASAA in PCOS subjects and effects of sera from normal and PCOS subjects (before and after metformin) on ASAA production (THP-1 macrophages) were also studied. METHODS AND RESULTS: Circulating ASAA (ELISA), subcutaneous and omental AT ASAA mRNA (RT-PCR) and protein (western blotting) were significantly higher in PCOS women (P<0.05). In AT explants, glucose significantly increased ASAA production and secretion (P<0.05, P<0.01). Furthermore, ASAA production (THP-1 macrophages) was significantly greater by sera from PCOS women compared to controls (P<0.01). ASAA protein production was significantly decreased by sera from PCOS women following 6 months of metformin treatment (P<0.05). After 6 months of metformin treatment, there was a significant decrease in circulating ASAA (P<0.05). Importantly, changes in intima media thickness were predictive of changes in circulating ASAA (P=0.034). CONCLUSION: Serum and AT ASAA are increased in PCOS women and are elevated by glucose. Metformin treatment decreases serum ASAA in these women. An adipose tissue-monocyte axis may be pivotal in the pathogenesis of inflammation and atherosclerosis. ASAA may be a valuable diagnostic marker in the management of dysmetabolic states including PCOS.

Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and obesity. Vaspin (visceral adipose tissue-derived serine protease inhibitor) levels increase with hyperinsulinemia and obesity. Currently, no data exists on vaspin in PCOS women. We therefore assessed mRNA and protein levels of vaspin, including circulating vaspin, from subcutaneous and omental adipose tissue of PCOS women and matched control subjects. Ex vivo regulation of adipose tissue vaspin and the effects of metformin treatment on circulating vaspin levels in PCOS subjects were also studied. RESEARCH DESIGN AND METHODS: Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of vaspin. Serum vaspin was quantified by enzyme-linked immunosorbent assay. The effects of d-glucose, insulin, and gonadal and adrenal steroids on adipose tissue vaspin were analyzed ex vivo. RESULTS: There were significantly higher levels of circulating vaspin (P < 0.05), vaspin mRNA (P < 0.05), and protein (P < 0.05) in omental adipose tissue of PCOS women. Interestingly, in omental adipose tissue explants, glucose significantly increased vaspin protein levels and secretion into conditioned media (P < 0.001). Also, after 6 months of metformin treatment, there was a significant decrease in serum vaspin levels in PCOS women (P < 0.001). Furthermore, multivariate regression analysis revealed that following metformin therapy, changes in circulating glucose levels were predictive of changes in serum vaspin levels (P = 0.014). CONCLUSIONS: We report, for the first time, elevated serum and omental adipose tissue levels of vaspin in overweight PCOS women and ex vivo regulation of vaspin, predominantly by glucose. More importantly, metformin treatment decreases serum vaspin levels, a novel observation.