Endometrial injury in women undergoing in vitro fertilisation (IVF).

BACKGROUND: Implantation of an embryo within the endometrial cavity is a critical step in the process of in vitro fertilisation (IVF). Previous research has suggested that endometrial injury (also known as endometrial scratching), defined as intentional damage to the endometrium, can increase the chance of pregnancy in women undergoing IVF. OBJECTIVES: To assess the effectiveness and safety of endometrial injury performed before embryo transfer in women undergoing in vitro fertilisation (IVF) including intracytoplasmic sperm injection (ICSI) and frozen embryo transfer. SEARCH METHODS: In June 2020 we searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, LILACS, DARE and two trial registries. We also checked the reference sections of relevant studies and contacted experts in the field for any additional trials. SELECTION CRITERIA: Randomised controlled trials comparing intentional endometrial injury before embryo transfer in women undergoing IVF, versus no intervention or a sham procedure. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Two independent review authors screened studies, evaluated risk of bias and assessed the certainty of the evidence by using GRADE (Grading of Recommendation, Assessment, Development and Evaluation) criteria. We contacted and corresponded with study investigators as required. Due to the high risk of bias associated with many of the studies, the primary analyses of all review outcomes were restricted to studies at a low risk of bias for selection bias and other bias. Sensitivity analysis was then performed including all studies. The primary review outcomes were live birth and miscarriage. MAIN RESULTS: Endometrial injury versus control (no procedure or a sham procedure) A total of 37 studies (8786 women) were included in this comparison. Most studies performed endometrial injury by pipelle biopsy in the luteal phase of the cycle before the IVF cycle. The primary analysis was restricted to studies at low risk of bias, and included eight studies. The effect of endometrial injury on live birth is unclear as the result is consistent with no effect, or a small reduction, or an improvement (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.98 to 1.28; participants = 4402; studies = 8; I2 = 15%, moderate-certainty evidence). This suggests that if the chance of live birth with IVF is usually 27%, then the chance when using endometrial injury would be somewhere between < 27% and 32%. Similarly, the effect of endometrial injury on clinical pregnancy is unclear (OR 1.08, 95% CI 0.95 to 1.23; participants = 4402; studies = 8; I2 = 0%, moderate-certainty evidence). This suggests that if the chance of clinical pregnancy from IVF is normally 32%, then the chance when using endometrial injury before IVF is between 31% and 37%. When all studies were included in the sensitivity analysis, we were unable to conduct meta-analysis for the outcomes of live birth and clinical pregnancy due to high risk of bias and statistical heterogeneity. Endometrial injury probably results in little to no difference in chance of miscarriage (OR 0.88, 95% CI 0.68 to 1.13; participants = 4402; studies = 8; I2 = 0%, moderate-certainty evidence), and this result was similar in the sensitivity analysis that included all studies. The result suggests that if the chance of miscarriage with IVF is usually 6.0%, then when using endometrial injury it would be somewhere between 4.2% and 6.8%. Endometrial injury was associated with mild to moderate pain (approximately 4 out of 10), and was generally associated with some minimal bleeding. The evidence was downgraded for imprecision due to wide confidence intervals and therefore all primary analyses were graded as moderate certainty. Higher versus lower degree of injury Only one small study was included in this comparison (participants = 129), which compared endometrial injury using two different instruments in the cycle prior to the IVF cycle: a pipelle catheter and a Shepard catheter. This trial was excluded from the primary analysis due to risk of bias. In the sensitivity analysis, all outcomes reported for this study were graded as very-low certainty due to risk of bias, and as such we were not able to interpret the study results. AUTHORS' CONCLUSIONS: The effect of endometrial injury on live birth and clinical pregnancy among women undergoing IVF is unclear. The results of the meta-analyses are consistent with an increased chance, no effect and a small reduction in these outcomes. We are therefore uncertain whether endometrial injury improves the chance of live birth or clinical pregnancy in women undergoing IVF. Endometrial injury does not appear to affect the chance of miscarriage. It is a somewhat painful procedure associated with a small amount of bleeding. In conclusion, current evidence does not support the routine use of endometrial injury for women undergoing IVF.

Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for assisted reproduction.

BACKGROUND: Subfertility is a condition found in up to 15% of couples of reproductive age. Gamete micromanipulation, such as intracytoplasmic sperm injection (ICSI), is very useful for treating couples with compromised sperm parameters. An alternative method of sperm selection has been described; the spermatozoa are selected under high magnification (over 6000x) and used for ICSI. This technique, named intracytoplasmic morphologically selected sperm injection (IMSI), has a theoretical potential to improve reproductive outcomes among couples undergoing assisted reproduction techniques (ART). However, our previous version of this Cochrane Review was unable to find evidence that supported this possible beneficial effect. This is an update of Teixeira 2013. OBJECTIVES: To identify, appraise, and summarise the available evidence regarding efficacy and safety of IMSI compared to ICSI in couples undergoing ART. SEARCH METHODS: We searched for randomised controlled trials (RCTs) in these electronic databases: the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, and in these trial registers: ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We also handsearched the reference lists of included studies and similar reviews. We performed the last electronic search on 18 November 2019. SELECTION CRITERIA: We only considered RCTs that compared ICSI and IMSI; we did not include quasi-randomised trials. We considered studies that permitted the inclusion of the same participant more than once (cross-over or per cycle trials) only if data regarding the first treatment of each participant were available. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, and assessment of the risk of bias and quality of the evidence; we solved disagreements by consulting a third review author. We corresponded with study investigators to resolve any queries, as required. MAIN RESULTS: The updated search retrieved 535 records; we included 13 parallel-designed RCTs comparing IMSI and ICSI (four studies were added since the previous version), comprising 2775 couples (IMSI = 1256; ICSI = 1519). We are uncertain if IMSI improves live birth rates (risk ratio (RR) 1.11, 95% confidence interval (CI) 0.89 to 1.39; 5 studies, 929 couples; I² = 1%), miscarriage rates per couple (RR 1.07, 95% CI 0.78 to 1.48; 10 studies, 2297 couples; I² = 0%, very-low quality evidence), and miscarriage rate per pregnancy (RR 0.90, 95% CI 0.68 to 1.20; 10 studies, 783 couples; I² = 0%, very-low quality evidence). We are uncertain if IMSI improves clinical pregnancy rates (RR 1.23, 95% CI 1.11 to 1.37; 13 studies, 2775 couples; I² = 47%, very-low quality evidence). None of the included studies reported congenital abnormalities. We judged the evidence for all outcomes to be of very low-quality. We downgraded the quality of the evidence due to limitations of the included studies (risk of bias), inconsistency of results, and a strong indication of publication bias. AUTHORS' CONCLUSIONS: The current evidence from randomised controlled trials does not support or refute the clinical use of intracytoplasmic sperm injection (intracytoplasmic morphologically selected sperm injection (IMSI). We are very uncertain of the chances of having a live birth and of the risk of having a miscarriage. We found very low-quality evidence that IMSI may increase chances of a clinical pregnancy, which means that we are still very uncertain about any real difference. We did not find any trials reporting on the risk of congenital abnormalities. Well-designed and sufficiently powered trials are still required.

Inter-Rater Reliability of Air/Saline HyCoSy, HyFoSy and HyFoSy Combined With Power Doppler for Screening Tubal Patency.

PURPOSE: To estimate the inter-observer reliability and agreement of offline analyses of three different ultrasound techniques for assessing tubal patency. METHODS: 100 tubes (n = 100) in 50 women were evaluated for tubal patency between November 2013 and July 2015 using ultrasound as index tests and laparoscopy as the reference standard. Three different ultrasound techniques were applied: two-dimensional grayscale ultrasound using air + saline as the contrast media (2D-HyCoSy); two- and three-dimensional grayscale ultrasound using foam as the contrast media (2 D/3D-HyFoSy); and the same technique but adding bi-directional power Doppler (2 D/3D-Doppler-HyFoSy). The videos containing full standardized exams using these three techniques were split into three parts, anonymized, encoded, randomized and reassessed in Nov. 2015 by two observers who assessed tubal patency using standardized criteria. These observers were blinded to any clinical information and each other's results. Proportions of observed agreement (po) and Cohen's Kappa (κ) including the 95 % confidence intervals (CI) were calculated. RESULTS: The inter-observer reliability/agreement in 2 D/3D-Doppler-HyFoSy (po = 0.99, κ = 0.95, 95 % CI: 0.93 - 0.97) was higher compared to 2D-air/saline-HyCoSy (po = 0.83, κ = 0.55, 95 % CI: 0.40 - 0.68) and 2 D/3D-HyFoSy (po = 0.92, κ = 0.67, 95 % CI: 0.54 - 0.76). CONCLUSION: The inter-observer reliability and agreement of the diagnosis of tubal patency evaluating stored videos are improved when foam and power Doppler are used during acquisition. Therefore, this technique may be preferred to minimize misclassification and misdiagnosis.

Pain Intensity During Ultrasound Assessment of Uterine Cavity and Tubal Patency With and Without Painkillers: Prospective Observational Study.

STUDY OBJECTIVE: To determine the pain intensity and incidence of mild to severe pain during the ultrasound assessment of the uterine cavity and tubal patency using saline, air and saline, and foam as contrasts with and without painkiller. DESIGN: Prospective observational study (Canadian Task Force classification II-1). SETTING: Private clinic. PATIENTS: Three hundred infertile women who were consecutively submitted to uterine cavity and tubal patency assessment by ultrasound using saline, air, and foam in single exam between October 2012 and November 2013. INTERVENTIONS: No painkillers were used until March 2013 when we started offering an effervescent codeine tablet containing paracetamol 500 mg and codeine phosphate 30 mg approximately 1 hour before the procedure. MEASUREMENTS AND MAIN RESULTS: Pain intensity measured with an 11-point (0-10) numerical rating scale and incidence of moderate/severe levels of pain (numerical rating scale > 3) during the main components of the procedure (speculum insertion, catheter insertion, saline infusion, air and saline infusion, foam infusion, and after the procedure [0 minutes, 15 minutes, 30 minutes, and 24 hours]) were assessed. The incidence of moderatesevere pain was significantly lower in women using painkillers considering any moment of the procedure: 49 of 175 (28%) versus 65 of 125 (52%); relative risk, .54; 95% confidence interval, .40-.72; p < .001; number needed to treat, 4. Less women presented with moderate/severe pain during air and saline compared with foam infusion: 31 of 300 (10%) versus 75 of 300 (25%); p < .001; relative risk, .41, 95% confidence interval, .28-.61. CONCLUSION: The incidence of moderate/severe pain during the ultrasound assessment of the uterine cavity and tubal patency is common. Our results suggest that using paracetamol + codeine before the procedure reduces the pain level, but randomized controlled trials are required.

Endometrial injury for pregnancy following sexual intercourse or intrauterine insemination.

BACKGROUND: Intentional endometrial injury is currently being proposed as a technique to improve the probability of pregnancy in women undergoing assisted reproductive technologies (ART) such as in vitro fertilisation (IVF). Endometrial injury is often performed by pipelle biopsy or a similar technique, and is a common, simple, gynaecological procedure that has an established safety profile. However, it is also known to be associated with a moderate degree of discomfort/pain and requires an additional pelvic examination. The effectiveness of this procedure outside of ART, in women or couples attempting to conceive via sexual intercourse or with low complexity fertility treatments such as intrauterine insemination (IUI) and ovulation induction (OI), remains unclear. OBJECTIVES: To evaluate the effectiveness and safety of intentional endometrial injury in subfertile women and couples attempting to conceive through sexual intercourse or intrauterine insemination (IUI). SEARCH METHODS: We searched the Cochrane Gyanecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, DARE, ISI Web of Knowledge and ClinicalTrials.gov; as well as reference lists of relevant reviews and included studies. We performed the searches from inception to 31 October 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated any kind of intentional endometrial injury in women planning to undergo IUI or attempting to conceive spontaneously (with or without OI) compared to no intervention, a mock intervention or intentional endometrial injury performed at a different time or to a higher/lower degree. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, extracted data and assessed trial quality using GRADE methodology. The primary outcomes were live birth/ongoing pregnancy and pain experienced during the procedure. Secondary outcomes were clinical pregnancy, miscarriage, ectopic pregnancy, multiple pregnancy and bleeding secondary to the procedure. We combined data to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I(2) statistic. MAIN RESULTS: Nine trials, which included a total of 1512 women, met the inclusion criteria of this Cochrane review. Most of these studies included women with unexplained infertility. In seven studies the women were undergoing IUI and in two studies the women were trying to conceive from sexual intercourse. Eight trials compared intentional endometrial injury with no injury/placebo procedure; of these two trials also compared intentional endometrial injury in the cycle prior to IUI with intentional endometrial injury in the IUI cycle. One trial compared higher vs. lower degree of intentional endometrial injury. Intentional endometrial injury vs. either no intervention or a sham procedureWe are uncertain whether endometrial injury improves live birth/ongoing pregnancy as the quality of the evidence has been assessed as very low (risk ratio (RR) 2.22, 95% confidence interval (CI) 1.56 to 3.15; six RCTs, 950 participants; I² statistic = 0%, very low quality evidence). When we restricted the analysis to only studies at low risk of bias the effect was imprecise and the evidence remained of very low quality (RR 2.64, 95% CI 1.03 to 6.82; one RCT, 105 participants; very low quality evidence). Endometrial injury may improve clinical pregnancy rates however the evidence is of low quality (RR 1.98, 95% CI 1.51 to 2.58; eight RCTs, 1180 participants; I² statistic = 0%, low quality evidence).The average pain experienced by participants undergoing endometrial injury was 6/10 on a zero-10 visual analogue scale (VAS)(standard deviation = 1.5). However, only one study reported this outcome. Higher vs. lower degree of intentional endometrial injuryWhen we compared hysteroscopy with endometrial injury to hysteroscopy alone, there was no evidence of a difference in ongoing pregnancy rate (RR 1.29, 95% CI 0.71 to 2.35; one RCT, 332 participants; low quality evidence) or clinical pregnancy rate (RR 1.15, 95% CI 0.66 to 2.01; one RCT, 332 participants, low quality evidence). This study did not report the primary outcome of pain during the procedure. Timing of intentional endometrial injuryWhen endometrial injury was performed in the cycle prior to IUI compared to the same cycle as the IUI, there was no evidence of a difference in ongoing pregnancy rate (RR 0.65, 95% CI 0.37 to 1.16, one RCT, 176 participants; very low quality evidence) or clinical pregnancy rate (RR 0.82, 95% CI 0.50 to 1.36; two RCTs, 276 participants; very low quality evidence). Neither of these studies reported the primary outcome of pain during the procedure.In all three comparisons there was no evidence of an effect on miscarriage, ectopic pregnancy or multiple pregnancy. No studies reported bleeding secondary to the procedure. AUTHORS' CONCLUSIONS: It is uncertain whether endometrial injury improves the probability of pregnancy and live birth/ongoing pregnancy in women undergoing IUI or attempting to conceive via sexual intercourse. The pooled results should be interpreted with caution as we graded the quality of the evidence as either low or very low. The main reasons we downgraded the quality of the evidence were most included studies were at a high risk of bias and had an overall low level of precision. Further well-conducted RCTs that recruit large numbers of participants and minimise internal bias are required to confirm or refute these findings.

Blastocyst culture using single versus sequential media in clinical IVF: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The purpose of this study was to undertake a review of the available evidence comparing the use of a single medium versus sequential media for embryo culture to the blastocyst stage in clinical IVF. METHODS: We searched the Cochrane Central, PubMed, Scopus, ClinicalTrials.gov, Current Controlled Trials and WHO International Clinical Trials Registry Platform to identify randomized controlled trials comparing single versus sequential media for blastocyst culture and ongoing pregnancy rate. Included studies randomized either oocytes/zygotes or women. Eligible oocyte/zygote studies were analyzed to assess the risk difference (RD) and 95 % confidence intervals (CI) between the two media systems; eligible woman-based studies were analyzed to assess the risk ratio (RR) and 95 % CI for clinical pregnancy rate. RESULTS: No differences were observed between single and sequential media for either ongoing pregnancy per randomized woman (relative risk (RR) = 0.9, 95 % CI = 0.7 to 1.3, two studies including 246 women, I 2 = 0 %) or clinical pregnancy per randomized woman (RR = 1.0, 95 % CI = 0.7 to 1.4, one study including 100 women); or miscarriage per clinical pregnancy: RR = 1.3, 95 % CI = 0.4 to 4.3, two studies including 246 participants, I 2 = 0 %). Single media use was associated with an increase blastocyst formation per randomized oocyte/zygote (relative distribution (RD) = +0.06, 95 % CI = +0.01 to +0.12, ten studies including 7455 oocytes/zygotes, I 2 = 83 %) but not top/high blastocyst formation (RD = +0.05, 95 % CI = -0.01 to +0.11, five studies including 3879 oocytes/zygotes, I 2 = 93 %). The overall quality of the evidence was very low for all these four outcomes. CONCLUSIONS: Although using a single medium for extended culture has some practical advantages and blastocyst formation rates appear to be higher, there is insufficient evidence to recommend either sequential or single-step media as being superior for the culture of embryos to days 5/6. Future studies comparing these two media systems in well-designed trials should be performed.

Artificial oocyte activation to improve reproductive outcomes in women with previous fertilization failure: a systematic review and meta-analysis of RCTs.

STUDY QUESTION: In couples with previous fertilization failure, are reproductive outcomes improved using ICSI followed by artificial oocyte activation (ICSI-AOA) compared with conventional ICSI? SUMMARY ANSWER: There is insufficient evidence available from RCTs to judge the efficacy and safety of ICSI-AOA for couples with previous fertilization failure. WHAT IS KNOWN ALREADY: In cases with previous low fertilization rates or total fertilization failure using ICSI due to sperm-related, oocyte activation deficiency, several methods of AOA have been described, which employ mechanical, electrical or chemical stimuli. Reported fertilization and pregnancy rates appear to be improved after ICSI-AOA compared with conventional ICSI; however, the small studies performed to date make it difficult to assess the clinical efficacy or safety of AOA. STUDY DESIGN, SIZE, AND DURATION: The present systematic review and meta-analysis identified RCTs that compared ICSI-AOA and conventional ICSI. The last electronic search was conducted in August 2014 and there was no limitation regarding language, publication date, or publication status. We included studies that randomized either oocytes or women and included them in two different parts of this review: a women-based review and an oocyte-based review. For the women-based review, the primary outcome of effectiveness was live birth per randomized woman and the primary outcome for safety was congenital anomalies per clinical pregnancy. For the oocyte-based review, the primary outcome was embryo formation per oocyte randomized. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: Record screening and data extraction were performed independently by two authors and risk of bias was assessed by three authors. The effects of ICSI-AOA compared with conventional ICSI were summarized as risk ratio (RR) and the precision of the estimates was evaluated by the 95% confidence interval (CI). MAIN RESULTS AND THE ROLE OF CHANCE: A total of 14 articles were assessed for eligibility and 9 included in the meta-analysis: 2 studies comprised the woman-based review (n = 168 women) and 7 studies the oocyte-based review (n = 4234 oocytes). Only four studies evaluated AOA due to fertilization failure after conventional ICSI: these were included in the quantitative analysis. In two studies evaluating couples with a history of fertilization failure in a previous cycle, ICSI-AOA was associated with an increase in the proportion of cleavage stage embryos (RR 5.44, 95% CI 2.98-9.91) and top/high quality cleavage stage embryos (RR 10.02, 95% CI 2.45-40.95). There was no evidence of effect on fertilization rate (RR 2.97, 95% CI 0.84-10.48). In the two studies that evaluated ICSI-AOA as a rescue method for unfertilized oocytes after conventional ICSI, ICSI-AOA was associated with an increase in fertilization (RR 8.26, 95% CI 1.28-53.32, P = 0.03) and cleavage rates (RR 8.65, 95% CI 2.28-32.77) although there was no significant effect on the likelihood of blastocyst formation (RR 1.97, 95% CI 0.11-34.99). The remaining five studies evaluated ICSI-AOA for reasons other than fertilization failure and were excluded. LIMITATIONS AND REASONS FOR CAUTION: The majority of the studies were not considered to be similar enough for meta-analysis due to different AOA methods and patient inclusion criteria, thus limiting the possibility of pooling studies and achieving a more robust conclusion. Only two studies examined ICSI-AOA in couples with previous fertilization failure, and only one of these included couples with proven male-related, oocyte activation deficiency, which is the primary indication for AOA. The resulting evidence was considered to be of very low quality and should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: There is insufficient evidence available from the currently available RCTs to judge the efficacy or safety of ICSI-AOA on key reproductive outcomes in couples with previous fertilization failure. Such interventions should be further examined by well-designed RCTs before the introduction of ICSI-AOA as a standard treatment. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained. No competing interests to declare. REGISTRATION NUMBER: PROSPERO CRD42014007445.

Endometrial injury in women undergoing assisted reproductive techniques.

BACKGROUND: Implantation of an embryo within the endometrial cavity is a critical step in assisted reproductive techniques (ART). Previous research has suggested that endometrial injury - intentional damage to the endometrium - can increase the probability of pregnancy in women undergoing ART. OBJECTIVES: To assess the effectiveness and safety of endometrial injury performed before embryo transfer in women undergoing ART. SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Latin American Caribbean Health Sciences Literature (LILACS) and ClinicalTrials.gov. The original search was performed in November 2011, and further searches were done in March 2014 and January 2015. SELECTION CRITERIA: Randomised controlled trials comparing intentional endometrial injury before embryo transfer in women undergoing ART, versus no intervention or a sham procedure. DATA COLLECTION AND ANALYSIS: Two independent review authors screened studies and extracted data which were checked by a third review author. Two review authors independently assessed risk of bias. We contacted and corresponded with study investigators as required and analysed data using risk ratio (RR) and a random-effects model. We assessed the quality of the evidence by using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. MAIN RESULTS: We included 14 trials that included 1063 women in the intervention groups and 1065 women in the control groups. Thirteen studies compared endometrial injury performed between day 7 of the previous cycle and day 7 of the embryo transfer (ET) cycle versus no injury, and one study compared endometrial injury on the day of oocyte retrieval versus no injury. Overall, eight of the 14 included studies were deemed to be at high risk of bias in at least one domain.In studies comparing endometrial injury performed between day 7 of the previous cycle and day 7 of the ET cycle versus no intervention or a sham procedure, endometrial injury was associated with an increase in live birth or ongoing pregnancy rate: RR 1.42, 95% confidence interval (CI) 1.08 to 1.85; P value 0.01; nine RCTs; 1496 women; I² = 53%; moderate-quality evidence. In other words, moderate-quality evidence suggests that if 26% of women achieve live birth without endometrial injury, between 28% and 48% will achieve live birth with endometrial injury. A sensitivity analysis removing the studies at high risk of bias showed no difference in effect.There was no evidence of an effect on miscarriage, however the evidence is of low-quality: RR 0.99, 95% CI 0.63 to 1.53; P value 0.06; eight RCTs; 500 clinical pregnancies; I² = 10%; low-quality evidence.Endometrial injury was also associated with an increased clinical pregnancy rate: RR 1.34, 95% CI 1.21 to 1.61; P value 0.002; 13 RCTs; 1972 women; I² = 45%; moderate-quality evidence. This suggests that if 30% of women achieve clinical pregnancy without endometrial injury, between 33% and 48% will achieve clinical pregnancy with this intervention.Endometrial injury was associated with increased pain, however the evidence was of very low quality. One study reported pain on a VAS scale: MD 4.60, 95% CI 3.98 to 5.22; P value < 0.00001; one RCT; 158 women. Two studies reported the number of pain complaints after the procedure; one recorded no events in either group, and the other reported that endometrial injury increased pain complaints: OR 8.65, 95% CI 2.49 to 30.10; P value 0.0007; one RCT; 101 women.Results from the only randomised controlled trial (RCT) comparing endometrial injury on the day of oocyte retrieval versus no injury, reported that this endometrial injury markedly decreased live birth (RR 0.31, 95% CI 0.14 to 0.69; P value 0.004; 156 women; low-quality evidence) and clinical pregnancy (RR 0.36, 95% CI 0.18 to 0.71; P value 0.003; one RCT; 156 women; low-quality evidence). AUTHORS' CONCLUSIONS: Moderate-quality evidence indicates that endometrial injury performed between day 7 of the previous cycle and day 7 of the embryo transfer (ET) cycle is associated with an improvement in live birth and clinical pregnancy rates in women with more than two previous embryo transfers. There is no evidence of an effect on miscarriage, multiple pregnancy or bleeding. The procedure is mildly painful. Endometrial injury on the day of oocyte retrieval is associated with a reduction of clinical and ongoing pregnancy rates.Although current evidence suggests some benefit of endometrial injury, we need evidence from well-designed trials that avoid instrumentation of the uterus in the preceding three months, do not cause endometrial damage in the control group, stratify the results for women with and without recurrent implantation failure (RIF) and report live birth.

Add-back therapy with GnRH analogues for uterine fibroids.

BACKGROUND: Uterine fibroids (also known as leiomyomas) are the most common benign pelvic tumours among women. They may be asymptomatic, or may be associated with pelvic symptoms such as bleeding and pain. Medical treatment of this condition is limited and gonadotropin-releasing hormone (GnRH) analogues are the most effective agents. Long-term treatment with such agents, however, is restricted due to their adverse effects. The addition of other medications during treatment with GnRH analogues, a strategy known as add-back therapy, may limit these side effects. There is concern, however, that add-back therapy may also limit the efficacy of the GnRH analogues and that it may not be able to completely prevent their adverse effects. OBJECTIVES: To assess the short-term (within 12 months) effectiveness and safety of add-back therapy for women using GnRH analogues for uterine fibroids associated with excessive uterine bleeding, pelvic pain, or urinary symptoms. SEARCH METHODS: We searched electronic databases including the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, CENTRAL, MEDLINE, PubMed, EMBASE, LILACS, CINAHL, PsycINFO; and electronic registries of ongoing trials including ClinicalTrials.gov, Current Controlled Trials, World Health Organization (WHO) International Clinical Trials Registry Platform. All searches were from database inception to 16 June 2014. SELECTION CRITERIA: Randomized controlled trials (RCTs) that included women with uterine fibroids experiencing irregular or intense uterine bleeding, cyclic or non-cyclic pelvic pain, or urinary symptoms, and that compared treatment with a GnRH analogue plus add-back therapy versus a GnRH analogue alone or combined with placebo were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the identified titles and abstracts for potentially eligible records. Two review authors reviewed eligible studies and independently extracted data. Two authors independently assessed the studies' risk of bias. They assessed the quality of the evidence using GRADE criteria. MAIN RESULTS: Fourteen RCTs were included in the review. Data were extracted from 12 studies (622 women). The primary outcome was quality of life (QoL).Add-back therapy with medroxyprogesterone (MPA): no studies reported QoL or uterine bleeding. There was no evidence of effect in relation to bone mass (standardized mean difference (SMD) 0.38, 95% confidence interval (CI) -0.62 to 1.38, 1 study, 16 women, P = 0.45, low quality evidence) and MPA was associated with a larger uterine volume (mean difference (MD) 342.19 cm(3), 95% CI 77.58 to 606.80, 2 studies, 32 women, I(2) = 0%, low quality evidence).Tibolone: this was associated with a higher QoL but the estimate was imprecise and the effect could be clinically insignificant, small or large (SMD 0.47, 95% CI 0.09 to 0.85, 1 study, 110 women, P = 0.02, low quality evidence). It was also associated with a decreased loss of bone mass, which could be insignificant, small or moderate (SMD 0.36, 95% CI 0.03 to 0.7, 3 studies, 160 women, I(2) = 7%, moderate quality evidence). Tibolone may, however, have been associated with larger uterine volumes (MD 23.89 cm(3), 95% CI= 8.13 to 39.66, 6 studies, 365 women, I(2) = 0%, moderate quality evidence) and more uterine bleeding (results were not combined but three studies demonstrated greater bleeding with tibolone while two other studies demonstrated no bleeding in either group). Four studies (268 women; not pooled owing to extreme heterogeneity) reported a large benefit on vasomotor symptoms in the tibolone group.Raloxifene: there was no evidence of an effect on QoL (SMD 0.11, 95% CI -0.57 to 0.34, 1 study, 74 women, P = 0.62, low quality evidence), while there was a beneficial impact on bone mass (SMD 1.01, 95% CI 0.57 to 1.45, 1 study, 91 women, P < 0.00001, low quality evidence). There was no clear evidence of effect on uterine volume (MD 27.1 cm(3), 95% CI -17.94 to 72.14, 1 study, 91 women, P = 0.24, low quality evidence), uterine bleeding or severity of vasomotor symptoms (MD 0.2 hot flushes/day, 95% CI -0.34 to 0.74, 1 study, 91 women, P = 0.46, low quality evidence).Estriol: no studies reported QoL, uterine size, uterine bleeding or vasomotor symptoms. Add-back with estriol may have led to decreased loss of bone mass, from results of a single study (SMD 3.93, 95% CI 1.7 to 6.16, 1 study, 12 women, P = 0.0005, low quality evidence).Ipriflavone: no studies reported QoL, uterine size or uterine bleeding. Iproflavone was associated with decreased loss of bone mass in a single study (SMD 2.71, 95% CI 2.14 to 3.27, 1 study, 95 women, P < 0.00001, low quality evidence); there was no evidence of an effect on the rate of vasomotor symptoms (RR 0.67, 95% Cl 0.44 to 1.02, 1 study, 95 women, P = 0.06, low quality evidence).Conjugated estrogens: no studies reported QoL, uterine size, uterine bleeding or vasomotor symptoms. One study suggested that adding conjugated estrogens to GnRH analogues resulted in a larger decrease in uterine volume in the placebo group (MD 105.2 cm(3), 95% CI 27.65 to 182.75, 1 study, 27 women, P = 0.008, very low quality evidence).Nine of 12 studies were at high risk of bias in at least one domain, most commonly lack of blinding. All studies followed participants for a maximum of six months. This short-term follow-up is usually insufficient to observe any significant effect of the treatment on bone health (such as the occurrence of fractures), limiting the findings. AUTHORS' CONCLUSIONS: There was low or moderate quality evidence that tibolone, raloxifene, estriol and ipriflavone help to preserve bone density and that MPA and tibolone may reduce vasomotor symptoms. Larger uterine volume was an adverse effect associated with some add-back therapies (MPA, tibolone and conjugated estrogens). For other comparisons, outcomes of interest were not reported or study findings were inconclusive.

Importance of Pulse Repetition Frequency Adjustment for 3- and 4-Dimensional Power Doppler Quantification.

OBJECTIVES: To determine the influence of the pulse repetition frequency (PRF) and wall motion filter on the 3-dimensional (3D) power Doppler vascularization-flow index (VFI) and volumetric pulsatility index (PI) obtained from spatiotemporal image correlation (STIC) data sets acquired from a common carotid artery of a healthy participant. METHODS: We acquired 11 STIC data sets, 1 for each PRF value ranging from 0.6 to 9.0 kHz. Vascularization-flow index and volumetric PI values were determined from the 440 static 3D data sets contained in these STIC data sets. Additionally, 3 sets of radio-frequency data were acquired for offline processing of different wall motion filter values for PRF values of 0.6, 3.3, and 10 kHz. RESULTS: We constructed VFI curves and observed 2 patterns: a flattened pattern with a low PRF and a triphasic pattern with a high PRF, correlating with the known pulsed wave Doppler profile of this vessel. Volumetric PI values were around 0 for low PRF settings and increased with increasing PRF. Analysis of the radiofrequency data showed that increasing wall motion filter values gradually filtered out the low-velocity power Doppler signals while retaining the higher-velocity ones, allowing the distinction of integrated power Doppler signal velocity throughout the cardiac cycle. CONCLUSIONS: We conclude that the PRF and wall motion filter dramatically influence 3D power Doppler indices and the volumetric PI, and the use of PRF values in which minimum VFI values are measured during the diastolic phase in the spectral Doppler wave may validate the use of the volumetric PI.

Combined oral contraceptive for treatment of women with uterine fibroids and abnormal uterine bleeding: a systematic review.

BACKGROUND/AIMS: We aimed at assessing the efficacy of combined oral contraceptives (COC) in treating women with uterine leiomyomata and heavy menstrual bleeding (HMB), as well as their effect over quality of life (QoL), tumor size, and hemoglobin concentration. METHODS: We searched various electronic databases and reference lists from all included studies. Randomized and nonrandomized controlled clinical trials were selected, and two trials were considered eligible - one randomized and one 'pseudo'-randomized. RESULTS: COCs performed less well than levonorgestrel-releasing intrauterine systems (LNG-IUSs) in controlling HMB, improving QoL, and improving the hemoglobin concentration, whereas the estimate was not sufficiently precise to define whether COCs were better than, equal to, or worse than LNG-IUSs in reducing tumor size. It must be stressed that these results are based on low-quality evidence, stemming from a single trial. Additionally, COCs were more effective than placebo in tumor size reduction, another conclusion based on another single study, considered as being at a high risk of bias and judged as very low-quality evidence. CONCLUSION: Evidence regarding the use of COCs as treatment for women with symptomatic fibroids is very scarce and of low quality, and we are very uncertain about the real efficacy of such treatment.

FSH replaced by low-dose hCG in the late follicular phase versus continued FSH for assisted reproductive techniques.

BACKGROUND: During controlled ovarian hyperstimulation (COH) follicle-stimulating hormone (FSH) is frequently used for several days to achieve follicular development. FSH is a relatively expensive drug, substantially contributing to the total expenses of assisted reproductive techniques (ART). When follicles achieve a diameter greater than 10 mm they start expressing luteinising hormone (LH) receptors. At this point, FSH might be replaced by low-dose human chorionic gonadotropin (hCG), which is less expensive. In addition to cost reduction, replacing FSH by low-dose hCG has a theoretical potential to reduce the incidence of ovarian hyperstimulation syndrome (OHSS). OBJECTIVES: To evaluate the effectiveness and safety of using low-dose hCG to replace FSH during the late follicular phase in women undergoing COH for assisted reproduction, compared to the use of a conventional COH protocol. SEARCH METHODS: We searched for randomised controlled trials (RCT) in electronic databases (Menstrual Disorders and Subfertility Group Specialized Register, CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), trials registers (ClinicalTrials.gov, Current Controlled Trials, World Health Organization International Clinical Trials Registry Platform), conference abstracts (ISI Web of knowledge), and grey literature (OpenGrey); additionally we handsearched the reference list of included studies and similar reviews. The last electronic search was performed in February 2013.. SELECTION CRITERIA: Only true RCTs comparing the replacement of FSH by low-dose hCG during late follicular phase of COH were considered eligible; quasi or pseudo-randomised trials were not included. Cross-over trials would be included only if data regarding the first treatment of each participant were available; trials that included the same participant more than once would be included only if each participant was always allocated to the same intervention and follow-up periods were the same in both/all arms, or if data regarding the first treatment of each participant were available. We excluded trials that sustained FSH after starting low-dose hCG and those that started FSH and low-dose hCG at the same time. DATA COLLECTION AND ANALYSIS: Study eligibility, data extraction, and assessment of the risk of bias were performed independently by two review authors, and disagreements were solved by consulting a third review author. We corresponded with study investigators in order to solve any query, as required. The overall quality of the evidence was assessed in a GRADE summary of findings table. MAIN RESULTS: The search retrieved 1585 records; from those five studies were eligible, including 351 women (intervention = 166; control = 185). All studies were judged to be at high risk of bias. All reported per-woman rather than per-cycle data.When use of low-dose hCG to replace FSH was compared with conventional COH for the outcome of live birth, confidence intervals were very wide and findings were compatible with appreciable benefit, no effect or appreciable harm for the intervention (RR 1.56, 95% CI 0.75 to 3.25, 2 studies, 130 women, I² = 0%, very-low-quality evidence). This suggests that for women with a 14% chance of achieving live birth using conventional COH, the chance of achieving live birth using low-dose hCG would be between 10% and 45%.Similarly confidence intervals were very wide for the outcome of OHSS and findings were compatible with benefit, no effect or harm for the intervention (OR 0.30, 95% CI 0.06 to 1.59, 5 studies, 351 women, I² = 59%, very-low-quality evidence). This suggests that for women with a 3% risk of OHSS using conventional COH, the risk using low-dose hCG would be between 0% and 4%.The confidence intervals were wide for the outcome of ongoing pregnancy and findings were compatible with benefit or no effect for the intervention (RR 1.14, 95% CI 0.81 to 1.60, 3 studies, 252 women, I² = 0%, low-quality evidence). This suggests that for women with a 32% chance of achieving ongoing pregnancy using conventional COH, the chance using low-dose hCG would be between 27% and 53%.The confidence intervals were wide for the outcome of clinical pregnancy and findings were compatible with benefit or no effect for the intervention (RR 1.19, 95% CI 0.92 to 1.55, 5 studies, 351 women, I² = 0%, low-quality evidence). This suggests that for women with a 35% chance of achieving clinical pregnancy using conventional COH, the chance using low-dose hCG would be between 32% and 54%.The confidence intervals were very wide for the outcome of miscarriage and findings were compatible with benefit, no effect or harm for the intervention (RR 1.08, 95% CI 0.50 to 2.31, 3 studies, 127 pregnant women, I² = 0%, very-low-quality evidence). This suggests that for pregnant women with a 16% risk of miscarriage using conventional COH, the risk using low-dose hCG would be between 8% and 36%.The findings for the outcome of FSH consumption were compatible with benefit for the intervention (MD -639 IU, 95% CI -893 to -385, 5 studies, 333 women, I² = 88%, moderate-quality evidence).The findings for the outcome of number of oocytes retrieved were compatible with no effect for the intervention (MD -0.12 oocytes, 95% CI -1.0 to 0.8 oocytes, 5 studies, 351 women, I² = 0%, moderate-quality evidence). AUTHORS' CONCLUSIONS: We are very uncertain of the effect on live birth, OHSS and miscarriage of using low-dose hCG to replace FSH during the late follicular phase of COH in women undergoing ART, compared to the use of conventional COH. The current evidence suggests that this intervention does not reduce the chance of ongoing and clinical pregnancy; and that it is likely to result in an equivalent number of oocytes retrieved expending less FSH. More studies are needed to strengthen the evidence regarding the effect of this intervention on important reproductive outcomes.

Hormone therapy for sexual function in perimenopausal and postmenopausal women.

BACKGROUND: The perimenopausal and postmenopausal periods are associated with many symptoms, including sexual complaints. OBJECTIVES: To assess the effect of hormone therapy (HT) on sexual function in perimenopausal and postmenopausal women. SEARCH METHODS: We searched for articles in the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, ClinicalTrials.gov, Current Controlled Trials, WHO International Clinical Trials Registry Platform, ISI Web of Knowledge and OpenGrey. The last search was performed in December 2012. SELECTION CRITERIA: We included randomised controlled trials comparing HT to either placebo or no intervention (control). We considered as HT estrogens alone; estrogens in combination with progestogens; synthetic steroids (for example tibolone); or selective estrogen receptor modulators (SERMs) (for example raloxifene, bazedoxifene). Studies of other drugs possibly used in the relief of menopausal symptoms were excluded. We included studies that evaluated sexual function using any validated assessment tool. The primary outcome was a composite score for sexual function and the scores for individual domains (arousal and sexual interest, orgasm, and pain) were secondary outcomes. Studies were selected by two authors independently. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two authors and checked by a third. Risk of bias assessment was performed independently by two authors. We contacted study investigators as required. Data were analysed using standardized mean difference (SMD) and relative risk (RR). We stratified the analysis by participant characteristics with regard to menopausal symptoms. The overall quality of the evidence for the primary outcome was evaluated using the GRADE criteria. MAIN RESULTS: The search retrieved 2351 records from which 27 studies (16,393 women) were included. The 'symptomatic or early post-menopausal' subgroup included nine studies: perimenopausal women (one study), up to 36 months postmenopause (one study), up to five years postmenopause (one study), experiencing vasomotor or other menopausal symptoms (five studies), or experiencing hot flushes and sexual dysfunction (one study). The 'unselected postmenopausal women' subgroup included 18 studies, which included women regardless of menopausal symptoms and permitted the inclusion of women with more than five years since the final menstrual period. No studies were restricted to women with sexual dysfunction. Only five studies evaluated sexual function as a primary outcome. Eighteen studies were deemed at high risk of bias, and the other nine studies were at unclear risk of bias. Twenty studies received commercial funding.Findings for sexual function (measured by composite score):For estrogens alone versus control, in symptomatic or early postmenopausal women the SMD and 95% CI were compatible with a small to moderate benefit in sexual function for the HT group (SMD 0.38, 95% CI 0.23 to 0.54, P < 0.00001, 3 studies, 699 women, I² = 55%, high-quality evidence). In unselected postmenopausal women, the 95% CI was compatible with no effect to a small benefit (SMD 0.16, 95% CI -0.02 to 0.34, P = 0.08, 2 studies, 478 women, I² = 44%, low-quality evidence). The subgroups were not pooled because of considerable heterogeneity.For estrogens combined with progestogens versus control, in symptomatic or early postmenopausal women the 95% CI was compatible with a small to moderate benefit for sexual function in the HT group (SMD 0.42, 95% CI 0.19 to 0.64, P = 0.0003, 1 study, 335 women, moderate-quality evidence). In unselected postmenopausal women, the 95% CI was compatible with no effect to a small benefit (SMD 0.09, 95% CI -0.02 to 0.20, P = 0.10, 3 studies, 1314 women, I² = 0%, moderate-quality evidence). The subgroups were not pooled because of considerable heterogeneity.For tibolone versus control, in symptomatic or early postmenopausal women the 95% CI was compatible with no effect to a small benefit for sexual function in the HT group (SMD 0.13, 95% CI 0.00 to 0.26, P = 0.05, 1 study, 883 women, low-quality evidence). In unselected postmenopausal women, the 95% CI was compatible with no effect to a moderate benefit (SMD 0.38, 95% CI 0.04 to 0.71, P = 0.03, 2 studies, 142 women, I² = 0%, low-quality evidence). In the combined analysis, the 95% CI was compatible with no effect to a small benefit (SMD 0.17, 95% CI 0.04 to 0.29, P = 0.008, 3 studies, 1025 women, I² = 20%).For SERMs versus control, in symptomatic or early postmenopausal women the 95% CI was compatible with no effect to a moderate benefit for sexual function in the HT group (SMD 0.23, 95% CI -0.04 to 0.50, P = 0.09, 1 study, 215 women, low-quality evidence). In unselected postmenopausal women, the 95% CI was compatible with small harm to a small benefit (SMD 0.04, 95% CI -0.20 to 0.29, P = 0.72, 1 study, 283 women, low-quality evidence). In the combined analysis, the 95% CI was compatible with no effect to a small benefit (SMD 0.13, 95% CI -0.05 to 0.31, P = 0.16, 2 studies, 498 women, I² = 2%).A comparison of SERMs combined with estrogens versus control was only evaluated in symptomatic or early postmenopausal women. The 95% CI was compatible with no effect to a small benefit for sexual function in the HT group (SMD 0.21, 95% CI 0.00 to 0.43, P = 0.05, 1 study, 542 women, moderate-quality evidence). AUTHORS' CONCLUSIONS: HT treatment with estrogens alone or in combination with progestogens was associated with a small to moderate improvement in sexual function, particularly in pain, when used in women with menopausal symptoms or in early postmenopause (within five years of amenorrhoea), but not in unselected postmenopausal women. Evidence regarding other HTs (synthetic steroids and SERMs) is of low quality and we are uncertain of their effect on sexual function. The current evidence does not suggest an important effect of tibolone or of SERMs alone or combined with estrogens on sexual function. More studies evaluating the effect of synthetic steroids, SERMS and the association of SERM + estrogens would improve the quality of the evidence for the effect of these treatments on sexual function in peri and postmenopausal women. Future studies should also evaluate the effect of HT solely among women with sexual complaints.

Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for assisted reproduction.

BACKGROUND: Subfertility is a condition found in up to 15% of couples of reproductive age. Gamete micromanipulation, such as intracytoplasmic sperm injection (ICSI), is very useful for treating couples with compromised sperm parameters. Recently a new method of sperm selection named 'motile sperm organelle morphology examination' (MSOME) has been described and the spermatozoa selected under high magnification (over 6000x) used for ICSI. This new technique, named intracytoplasmic morphologically selected sperm injection (IMSI), has a theoretical potential to improve reproductive outcomes among couples undergoing assisted reproduction techniques (ART). OBJECTIVES: To compare the effectiveness and safety of IMSI and ICSI in couples undergoing ART. SEARCH METHODS: We searched for randomised controlled trials (RCT) in electronic databases (Cochrane Menstrual Disorders and Subfertility Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), trials registers (ClinicalTrials.gov, Current Controlled Trials, World Health Organization International Clinical Trials Registry Platform), conference abstracts (ISI Web of knowledge), and grey literature (OpenGrey); in addition, we handsearched the reference lists of included studies and similar reviews. We performed the last electronic search on 8 May 2013. SELECTION CRITERIA: We considered only truly randomised controlled trials comparing ICSI and IMSI to be eligible; we did not include quasi or pseudo-randomised trials. We included studies that permitted the inclusion of the same participant more than once (cross-over or 'per cycle' trials) only if data regarding the first treatment of each participant were available. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, and assessment of the risk of bias and we solved disagreements by consulting a third review author. We corresponded with study investigators in order to resolve any queries, as required. MAIN RESULTS: The search retrieved 294 records; from those, nine parallel design studies were included, comprising 2014 couples (IMSI = 1002; ICSI = 1012). Live birth was evaluated by only one trial and there was no significant evidence of a difference between IMSI and ICSI (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.79 to 1.64, 1 RCT, 168 women, I(2) = not applicable, low-quality evidence). IMSI was associated with a significant improvement in clinical pregnancy rate (RR 1.29, 95% CI 1.07 to 1.56, 9 RCTs, 2014 women, I(2) = 57%, very-low-quality evidence). We downgraded the quality of this evidence because of imprecision, inconsistency, and strong indication of publication bias. We found no significant difference in miscarriage rate between IMSI and ICSI (RR 0.82, 95% CI 0.59 to 1.14, 6 RCTs, 552 clinical pregnancies, I(2) = 17%, very-low-quality evidence). None of the included studies reported congenital abnormalities. AUTHORS' CONCLUSIONS: Results from RCTs do not support the clinical use of IMSI. There is no evidence of effect on live birth or miscarriage and the evidence that IMSI improves clinical pregnancy is of very low quality. There is no indication that IMSI increases congenital abnormalities. Further trials are necessary to improve the evidence quality before recommending IMSI in clinical practice.

Influence of gain adjustment on 3-dimensional power Doppler indices and on spatiotemporal image correlation volumetric pulsatility indices using a flow phantom.

Spatiotemporal image correlation can be used to acquire 3-dimensional power Doppler information across a single cardiac cycle. Assessment and comparison of the systolic and diastolic components of the data sets allow measurement of the recently introduced "volumetric pulsatility index" (vPI) through algorithms comparable with those used in 2-dimensional Doppler waveform analysis. The vPI could potentially overcome the dependency on certain machine settings, such as power, color gain, pulse repetition frequency, and attenuation, since these factors would affect the power Doppler signal equally throughout the cardiac cycle. The objective of this study was to compare the effect of color gain on the vascularization index (VI), vascularization-flow index (VFI), and vPI using an in vitro flow phantom model. We separated gains into 3 bands: -8 to -1 (no noise), -1 to +5 (low noise), and +5 to +8 (obvious noise). The vPI was determined from the 3-dimensional VI or VFI using the formula vPI = (maximum - minimum)/mean. Using no-noise gains, we observed that although the VI and VFI increased linearly with gain, the vPI was substantially less dependent on this adjustment. The VI and VFI continued to increase linearly with gain, whereas the vPI decreased slightly using low-noise gains. When gain was increased above the lower limit of obvious noise (+5), the VI and VFI increased noticeably, and there were marked reductions in both vPI values. We conclude that the vPI is less affected by changes in color gain than the VI and VFI at no-noise gains.

Endometrial injury in women undergoing assisted reproductive techniques.

BACKGROUND: Implantation of an embryo within the endometrial cavity is a key step in assisted reproductive techniques (ART). It has been suggested that intentional endometrial injury, such as endometrial biopsy or curettage, prior to embryo transfer improves the chances of implantation and further development thereby increasing the likelihood of live birth. The effectiveness and safety of this procedure is, however, still unclear. OBJECTIVES: To assess the effectiveness and safety of endometrial injury performed prior to embryo transfer in women undergoing ART. SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), DARE, MEDLINE, EMBASE, CINAHL, LILACS, and ClinicalTrials.gov. The final search was performed in November 2011. SELECTION CRITERIA: Randomised controlled trials comparing any kind of intentional endometrial injury prior to embryo transfer in women undergoing ART with no intervention or with a simulated (mock) procedure that could not cause endometrial injury. DATA COLLECTION AND ANALYSIS: Data were extracted by one author and checked by a second. Assessment of the risk of bias was performed independently by two authors. We contacted and corresponded with study investigators as required. Data were analysed using Peto odds ratio (OR) and a fixed-effect model. MAIN RESULTS: A total of 591 women from five trials were included. Clinical pregnancy was reported by all five studies and the combined analysis for clinical pregnancy per woman showed substantial heterogeneity (I(2) = 95.9%). We therefore conducted a planned subgroup analysis including four trials in the subgroup 'injury in the previous cycle' and one trial in the subgroup 'injury on the day of oocyte retrieval'. In the subgroup 'injury in the previous cycle' the procedure was performed within one month before starting ovulation induction in all four trials. This intervention resulted in a significant increase in the odds of live birth (2 trials, Peto OR 2.46; 95% CI 1.28 to 4.72; I(2) = 0%) and clinical pregnancy (4 trials, Peto OR 2.61; 95% CI 1.71 to 3.97; I(2) = 0%). The odds of miscarriage per clinical pregnancy (1 trial, Peto OR 1.13; 95% CI 0.17 to 7.45) and multiple pregnancy per clinical pregnancy (1 trial, Peto OR 0.87; 95% CI 0.23 to 3.30) were very imprecise, limiting any meaningful conclusion. No study reported pain or bleeding. In the subgroup 'injury on the day of oocyte retrieval', the intervention resulted in a significant reduction in the odds of clinical pregnancy (1 trial, Peto OR 0.30; 95% CI 0.14 to 0.63) and ongoing pregnancy (1 trial, Peto OR 0.28; 95% CI 0.13 to 0.61). The single trial in this subgroup did not report any adverse effect outcomes. AUTHORS' CONCLUSIONS: Endometrial injury performed prior to the embryo transfer cycle improves clinical pregnancy and live birth rates in women undergoing ART. It is advisable not to perform endometrial injury on the day of oocyte retrieval because it appears to significantly reduce clinical and ongoing pregnancy rates. There is insufficient evidence regarding the effect of endometrial injury on multiple pregnancy or miscarriage and none on adverse events such as pain and bleeding.

Evaluation of ductus venosus and inferior vena cava by using multiple Doppler ultrasound parameters in healthy fetuses.

PURPOSE: The objective of this study was to describe multiple Doppler ultrasound parameters of ductus venosus and inferior vena cava in fetuses at gestational ages ranging from 22 to 38 weeks. STUDY DESIGN: In this prospective observational study, Doppler ultrasound exams were performed in 45 healthy fetuses at 22, 26, 34, and 38 weeks. Maximum venous velocity, minimum venous velocity, venous pulsatility index, and venous acceleration time (VAT) (defined as the time between minimum and maximum venous velocity) were evaluated at those gestational periods. RESULTS: Increase in the velocities and decrease in the pulsatility index were observed in these vessels throughout gestational age. The VAT increased with gestational age. CONCLUSIONS: The VAT, a Doppler parameter still not described elsewhere, increased during pregnancy could be related to a longer period of time needed to fill the atrium in bigger hearts. In this study, we provide reference values for VAT in healthy fetuses.

Ovarian hyperstimulation syndrome: pathophysiology and prevention.

PURPOSE: To review and discuss the pathophysiology and prevention strategies for ovarian hyperstimulation syndrome (OHSS), which is a condition that may occur in up to 20% of the high risk women submitted to assisted reproductive technology cycles. METHODS: The English language literature on these topics were reviewed through PubMed and discussed with emphasis on recent data. RESULTS: The role of estradiol, luteinizing hormone, human chorionic gonadotropin (hCG), inflammatory mediators, the renin-angiotensin system and vascular endothelial growth factor is discussed in the pathophysiology of OHSS. In addition we consider the prevention strategies, including coasting, administration of albumin, renin-angiotensin system blockage, dopamine agonist administration, non-steroidal anti-inflammatory administration, GnRH antagonist protocols, reducing hCG dosage, replacement of hCG and in vitro maturation of oocytes (IVM). CONCLUSIONS: Among the many prevention strategies that have been discussed, the current evidence points to the replacement of hCG by GnRH agonists in antagonist cycles and the performance of IVM procedures as the safest approaches.