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Objective: The detection of high-grade cervical intraepithelial neoplasia (CIN) amongst patients with low-grade cytology (LSIL) is challenging. This study evaluated the role of high-risk HPV (HR-HPV) DNA test and p16(INK4a) immunostaining in identifying women with LSIL cytology at risk of harboring CIN2 or worse (CIN2+) and the role of p16(INK4a) in the triage of a population of HR-HPV positive LSIL., Methods: We conducted a prospective study including women with LSIL cytology. Detection of HR-HPV was carried out by means of a polymerase chain reaction based assay. p16(INK4a) immunostaining was performed using the Dako CINtec cytology kit. All patients had colposcopically directed punch biopsies or large loop excision of the transformation zone of the cervix. The endpoint was detection of a biopsy-confirmed CIN2+., Results: A series of 126 women with LSIL cytology were included. HR-HPV test had sensitivity 75% and specificity 64% for an endpoint of CIN2+. p16(INK4a) had significantly higher specificity of 89% (p=0.0000) but low sensitivity of 42%. The role of p16(INK4a) immunostaining in the triage of LSIL positive for HR-HPV was also evaluated. p16(INK4a) triage had 70% positive predictive value (PPV); however, this was not significantly higher than the PPV (56%) of HR-HPV test alone (p=0.4)., Conclusions: The results indicate that HR-HPV or p16(INK4a) cannot be used as solitary markers for the assessment of LSIL. The addition of p16(INK4a) immunostaining led to an increase in HR-HPV specificity; however, the biomarker needs to be assessed further to establish its role as an adjunct test in the triage of LSIL., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: To investigate the hypothesis that women achieving pregnancy after two or more failed embryo transfers (ETs) of good quality embryos have increased incidence of preeclamptic toxemia (PET) or fetal growth restriction (FGR) compared with those conceiving in the first ET after in vitro fertilization (IVF)., Design: Case-control study., Setting: Tertiary infertility center., Patient(s): Women who underwent IVF at the St. Mary's Hospital, Manchester, between January 2000 and June 2008 and conceived in the first ET, versus those who conceived after two or more failed ETs., Intervention(s): Retrospective case-note review., Main Outcome Measure(s): Incidence of PET or FGR., Result(s): Case notes of 364 eligible patients were identified: 125 conceived after two or more failed ETs and 239 in the first ET. The incidence of the primary outcome (PET or FGR) for the total number of pregnancies showed no significant difference between cases and controls (age and multiplicity adjusted odds ratio 1.2, 95% confidence interval 0.5-3.0). There were no significant differences between case and control subjects for the secondary outcomes., Conclusion(s): This study failed to demonstrate that women conceiving after two or more unsuccessful ETs are at increased risk of PET or FGR. More studies are required to investigate the relationship further., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The detection of high-grade cervical intraepithelial neoplasia (CIN2 or worse) among patients with low-grade cytology (LSIL) is challenging. The aim of this study was to assess the efficacy of p16(INK4a) in the risk assessment of women with LSIL cytology., Methods: Consecutive liquid-based cytology specimens of 95 LSIL smears were selected and stained for p16(INK4a). All patients had colposcopically directed punch biopsies or large loop excision of the transformation zone of the cervix. The endpoint was detection of a biopsy-confirmed CIN2 or worse., Results: The overall sensitivity and specificity of p16(INK4a) for diagnosis of CIN2+ among LSIL smears were 41% and 86%, respectively. The positive predictive value of the biomarker was 62% and the negative predictive value 72%., Conclusions: The study shows that p16(INK4a) has low sensitivity but acceptable specificity for evaluation of LSIL smears harbouring high-grade lesions. The marker needs to be further assessed as an adjunct to other tests in an attempt to improve the triage of LSIL cytology smears.

Objective: To determine whether a policy of elective single-embryo transfer (e-SET) lowers the multiple birth rate without compromising the live birth rate., Design: Systematic review and meta-analysis., Setting: Tertiary referral center for reproductive medicine and IVF unit., Patient(s): None., Intervention(s): Searches of the Cochrane Controlled Trials Register, Meta-register for Randomized Controlled Trials (RCTs), EMBASE, MEDLINE, and SCISEARCH with no limitation on language and publication year, 1974 to 2008., Selection Criteria: randomized, controlled trials comparing e-SET with double-embryo transfer (DET) for live birth and multiple birth rates after in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI). Nonrandomized trials and studies that included only patients who had blastocyst transfer were excluded., Main Outcome Measure(s): The likelihood of live birth per patient and multiple birth per total number of live births. Other outcomes included implantation rate, pregnancy rate, miscarriage and ectopic pregnancy rates, clinical pregnancy rate, ongoing pregnancy rate per patient, and preterm delivery rate per live birth., Result(s): Six trials (n=1354 patients) were included in the meta-analysis. Compared with DET, the e-SET policy was associated with a statistically significant reduction in the probability of live birth (RR 0.62; 95% CI, 0.53-0.72) and multiple birth (RR 0.06; 95% CI, 0.02-0.18)., Conclusion(s): Elective-SET of embryos at the cleavage stage reduces the likelihood of live birth by 38% and multiple birth by 94%. Evidence from randomized, controlled trials suggests that increasing the number of e-SET attempts (fresh and/or frozen) results in a cumulative live birth rate similar to that of DET. Offering subfertile women three cycles of IVF will have a major impact on the uptake of an e-SET policy., (Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of surgical treatment of endometrioma on pregnancy rate and ovarian response to gonadotrophin stimulation in women undergoing IVF., Design: A systematic review and meta-analysis., Setting: Tertiary referral center for reproductive medicine., Patient(s): Subfertile women with endometrioma undergoing IVF., Intervention(s): Surgical removal of endometrioma or expectant management., Main Outcome Measure(s): Clinical pregnancy rate and ovarian response to gonadotrophins (number of gonadotrophin ampoules, peak E(2) levels, number of oocytes retrieved, and number of embryos available for transfer)., Result(s): A search of three electronic databases for articles published between January 1985 and November 2007 yielded 20 eligible studies. Meta-analysis was conducted for five studies that compared surgery vs. no treatment of endometrioma. There was no significant difference in clinical pregnancy rate between the treated and the untreated groups. Similarly, no significant difference was found between the two groups with regard to the outcome measures used to assess the response to controlled ovarian hyperstimulation with gonadotrophins., Conclusion(s): Collectively the available data in the literature show that surgical management of endometriomas has no significant effect on IVF pregnancy rates and ovarian response to stimulation compared with no treatment. Randomized controlled trials are needed before producing best-practice recommendations on this topic.

There is an ongoing debate over the optimal dose of urinary HCG (u-HCG) that can trigger final oocyte maturation, leading to higher IVF success rate without increasing the risk of ovarian hyperstimulation syndrome (OHSS). A systematic review was conducted of all studies that compared the effect of at least two doses of u-HCG for final oocyte maturation on IVF outcomes and on the incidence of OHSS. The primary outcome was the live birth rate, and the secondary end-points were the number of oocytes retrieved, fertilization, implantation and pregnancy rates, and the incidence of OHSS. Only two amongst the six included studies were randomized controlled trials (RCT). Meta-analytic pool was not feasible due to insufficient number of studies assessing the same outcome and significant heterogeneity. The majority of studies concluded that the clinical outcomes were similar between women receiving 5000 or 10,000 IU of u-HCG. The incidence of OHSS was not reduced in the high-risk population even with lower dose of u-HCG. Until large scale RCT addressing the clinical effectiveness and the adverse outcomes related to various doses of u-HCG are conducted, the dose of u-HCG for final oocyte maturation for women referred for IVF needs to be individualized.

Background: P16(INK4a) is a biomarker for transforming HPV infections that could act as an adjunct to current cytological and histological assessment of cervical smears and biopsies, allowing the identification of those women with ambiguous results that require referral to colposcopy and potentially treatment., Material and Methods: We conducted a systematic review of all studies that evaluated the use of p16(INK4a) in cytological or histological specimens from the uterine cervix. We also estimated the mean proportion of samples that were positive for p16(INK4a) in cytology and histology, stratified by the grade of the lesion., Results: Sixty-one studies were included. The proportion of cervical smears overexpressing p16(INK4a) increased with the severity of cytological abnormality. Among normal smears, only 12% (95% CI: 7-17%) were positive for the biomarker compared to 45% of ASCUS and LSIL (95% CI: 35-54% and 37-57%, respectively) and 89% of HSIL smears (95% CI: 84-95%). Similarly, in histology only 2% of normal biopsies (95% CI: 0.4-30%) and 38% of CIN1 (95% CI: 23-53%) showed diffuse staining for p16(INK4a) compared to 68% of CIN2 (95% CI: 44-92%) and 82% of CIN3 (95% CI: 72-92%)., Conclusion: Although there is good evidence that p16(INK4a) immunostaining correlates with the severity of cytological/histological abnormalities, the reproducibility is limited due to insufficiently standardized interpretation of the immunostaining. Therefore, a consensus needs to be reached regarding the evaluation of p16(INK4a) staining and the biomarker needs to be assessed in various clinical settings addressing specific clinical questions.

Background: Post-partum haemorrhage (PPH) is a major complication of delivery. Hysterectomy is commonly performed when medical treatment of PPH fails. We assessed the effectiveness of Bakri balloon tamponade, a non-surgical technique in the management of PPH., Aim(s): Our objective is to report our experience in the use of Bakri balloon in treating PPH., Method: A retrospective study of 15 patients who underwent Bakri balloon insertion after unsuccessful medical management of PPH., Results: Fifteen cases of PPH were managed with Bakri balloon insertion. It was effective in all cases of PPH after vaginal delivery and in four cases of caesarean section; the overall effectiveness was 80%., Conclusion: Insertion of Bakri balloon is a simple alternative procedure in the management of PPH. It should be consider before any further surgical intervention including hysterectomy. Junior doctors and midwives can effectively apply it. It can be used during transfer or while waiting for a surgical procedure to reduce blood loss.

Objective: To investigate the effect of luteal E(2) supplementation on the pregnancy rate of IVF/intracytoplasmic sperm injection (ICSI) cycles., Design: A systematic review and meta-analysis of all the randomized controlled trials (RCTs)., Setting: Tertiary referral center for reproductive medicine and IVF., Patient(s): Women undergoing IVF or ICSI using the GnRH agonist or GnRH antagonist protocol with hMG or FSH for controlled ovarian hyperstimulation., Intervention(s): Progesterone (P4) alone or combined with estradiol valerate for luteal phase support., Main Outcome Measure(s): Pregnancy and clinical pregnancy rates per ET., Result(s): An electronic search was conducted targeting all reports published between January 1960 and March 2007. Ten RCTs met the criteria for inclusion in the meta-analysis. There were no statistically significant differences with regard to the main outcome measures, ongoing pregnancy rate per ET, or implantation rate between the group of women who had combined E(2) and P4 therapy and those who had P4 supplementation alone., Conclusion(s): The addition of E(2) to P4 for luteal phase support in IVF/ICSI cycles has no beneficial effect on pregnancy rates. The data in the literature are, however, limited and heterogeneous, precluding the extraction of clear and definite conclusions. A large multicenter, properly designed RCT is needed to further clarify the role of luteal E(2) supplementation in IVF.

Purpose: This review presents the current knowledge on ovarian cancer screening (OCS) together with a cumulative evaluation of the efficacy across diverse screening approaches based on up-to-date results., Materials and Methods: An electronic literature search was conducted targeting reports on the effectiveness of the various screening strategies., Results: Twenty-two prospective studies, 18 cohorts and 4 randomised control trials (RCTs) were retrieved. Where possible, sensitivity, specificity and predictive values, as well as the number needed to treat for each cancer (NNT) and each stage I disease [NNT (I)] detected are reported., Conclusion: The multimodal approach that incorporates CA125 as a primary and ultrasound as a secondary test appears to be superior to other strategies. However, the conclusive end-point that would provide the acceptable level of evidence for the introduction of screening should be a reduction in mortality. Up-to-date, there is no such evidence to justify this.