Impact of overweight and obesity in the fetal cardiac function parameters in the second and third trimesters of pregnancy.

OBJECTIVE: To assess the impact of overweight and obesity in the second and third trimesters of pregnancy on fetal cardiac function parameters. METHODS: We performed a prospective cohort study of 374 singleton pregnant women between 20w0d and 36w6d divided into three groups: 154 controls (body mass index - BMI < 25 kg/m2), 140 overweight (BMI 25-30 kg/m2) and 80 obese (BMI ≥ 30 kg/m2). Fetal left ventricular (LV) modified myocardial performance index (Mod-MPI) was calculated according to the following formula: (isovolumetric contraction time + isovolumetric relaxation time)/ejection time. Spectral tissue Doppler was used to determine LV and right ventricular (RV) myocardial performance index (MPI'), peak myocardial velocity during systole (S'), early diastole (E'), and late diastole (A'). RESULTS: We found significant differences between the groups in maternal age (p < 0.001), maternal weight (p < 0.001), BMI (p < 0.001), number of pregnancies (p < 0.001), parity (p < 0.001), gestational age (p = 0.013), and estimated fetal weight (p = 0.003). Overweight pregnant women had higher LV Mod-MPI (0.046 versus 0.044 seconds, p = 0.009) and LV MPI' (0.50 versus 0.47 seconds, p < 0.001) than the control group. Obese pregnant women had higher RV E' than control (6.82 versus 6.33 cm/sec, p = 0.008) and overweight (6.82 versus 6.46 cm/sec, p = 0.047) groups. There were no differences in 5-min APGAR score < 7, neonatal intensive care unit admission, hypoglycemia and hyperglobulinemia between the groups. CONCLUSIONS: We observed fetal myocardial dysfunction in overweight and obese pregnant women with higher LV Mod-MPI, LV MPI' and RV E' compared to fetuses from normal weight pregnant women.

Hormone therapy for sexual function in perimenopausal and postmenopausal women.

BACKGROUND: The perimenopausal and postmenopausal periods are associated with many symptoms, including sexual complaints. This review is an update of a review first published in 2013. OBJECTIVES: We aimed to assess the effect of hormone therapy on sexual function in perimenopausal and postmenopausal women. SEARCH METHODS: On 19 December 2022 we searched the Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, ISI Web of Science, two trials registries, and OpenGrey, together with reference checking and contact with experts in the field for any additional studies. SELECTION CRITERIA: We included randomized controlled trials that compared hormone therapy to either placebo or no intervention (control) using any validated assessment tool to evaluate sexual function. We considered hormone therapy: estrogen alone; estrogen in combination with progestogens; synthetic steroids, for example, tibolone; selective estrogen receptor modulators (SERMs), for example, raloxifene, bazedoxifene; and SERMs in combination with estrogen. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. We analyzed data using mean differences (MDs) and standardized mean differences (SMDs). The primary outcome was the sexual function score. Secondary outcomes were the domains of sexual response: desire; arousal; lubrication; orgasm; satisfaction; and pain. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 36 studies (23,299 women; 12,225 intervention group; 11,074 control group), of which 35 evaluated postmenopausal women; only one study evaluated perimenopausal women. The 'symptomatic or early postmenopausal women' subgroup included 10 studies, which included women experiencing menopausal symptoms (symptoms such as hot flushes, night sweats, sleep disturbance, vaginal atrophy, and dyspareunia) or early postmenopausal women (within five years after menopause). The 'unselected postmenopausal women' subgroup included 26 studies, which included women regardless of menopausal symptoms and women whose last menstrual period was more than five years earlier. No study included only women with sexual dysfunction and only seven studies evaluated sexual function as a primary outcome. We deemed 20 studies at high risk of bias, two studies at low risk, and the other 14 studies at unclear risk of bias. Nineteen studies received commercial funding. Estrogen alone versus control probably slightly improves the sexual function composite score in symptomatic or early postmenopausal women (SMD 0.50, 95% confidence interval (CI) (0.04 to 0.96; I² = 88%; 3 studies, 699 women; moderate-quality evidence), and probably makes little or no difference to the sexual function composite score in unselected postmenopausal women (SMD 0.64, 95% CI -0.12 to 1.41; I² = 94%; 6 studies, 608 women; moderate-quality evidence). The pooled result suggests that estrogen alone versus placebo or no intervention probably slightly improves sexual function composite score (SMD 0.60, 95% CI 0.16 to 1.04; I² = 92%; 9 studies, 1307 women, moderate-quality evidence). We are uncertain of the effect of estrogen combined with progestogens versus placebo or no intervention on the sexual function composite score in unselected postmenopausal women (MD 0.08 95% CI -1.52 to 1.68; 1 study, 104 women; very low-quality evidence). We are uncertain of the effect of synthetic steroids versus control on the sexual function composite score in symptomatic or early postmenopausal women (SMD 1.32, 95% CI 1.18 to 1.47; 1 study, 883 women; very low-quality evidence) and of their effect in unselected postmenopausal women (SMD 0.46, 95% CI 0.07 to 0.85; 1 study, 105 women; very low-quality evidence). We are uncertain of the effect of SERMs versus control on the sexual function composite score in symptomatic or early postmenopausal women (MD -1.00, 95% CI -2.00 to -0.00; 1 study, 215 women; very low-quality evidence) and of their effect in unselected postmenopausal women (MD 2.24, 95% 1.37 to 3.11 2 studies, 1525 women, I² = 1%, low-quality evidence). We are uncertain of the effect of SERMs combined with estrogen versus control on the sexual function composite score in symptomatic or early postmenopausal women (SMD 0.22, 95% CI 0.00 to 0.43; 1 study, 542 women; very low-quality evidence) and of their effect in unselected postmenopausal women (SMD 2.79, 95% CI 2.41 to 3.18; 1 study, 272 women; very low-quality evidence). The observed heterogeneity in many analyses may be caused by variations in the interventions and doses used, and by different tools used for assessment. AUTHORS' CONCLUSIONS: Hormone therapy treatment with estrogen alone probably slightly improves the sexual function composite score in women with menopausal symptoms or in early postmenopause (within five years of amenorrhoea), and in unselected postmenopausal women, especially in the lubrication, pain, and satisfaction domains. We are uncertain whether estrogen combined with progestogens improves the sexual function composite score in unselected postmenopausal women. Evidence regarding other hormone therapies (synthetic steroids and SERMs) is of very low quality and we are uncertain of their effect on sexual function. The current evidence does not suggest the beneficial effects of synthetic steroids (for example tibolone) or SERMs alone or combined with estrogen on sexual function. More studies that evaluate the effect of estrogen combined with progestogens, synthetic steroids, SERMs, and SERMs combined with estrogen would improve the quality of the evidence for the effect of these treatments on sexual function in perimenopausal and postmenopausal women.

Endometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis.

BACKGROUND: In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed. OBJECTIVE AND RATIONALE: This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis. SEARCH METHODS: A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET. OUTCOMES: Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02-1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96-1.54]; OR 1.25 [95% CI 0.99-1.57]; OR 1.26 [95% CI 1.03-1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo transfers, treatment type, or infertility cause. WIDER IMPLICATIONS: This is the first meta-analysis based on IPD of more than 4000 participants, and it demonstrates that endometrial scratching may improve LB rates in women undergoing IVF/ICSI. Subgroup analysis for age, number of previous failed embryo transfers, treatment type, and infertility cause could not identify subgroups in which endometrial scratching performed better or worse. The timing of endometrial scratching may play a role in its effectiveness. The use of endometrial scratching in clinical practice should be considered with caution, meaning that patients should be properly counseled on the level of evidence and the uncertainties.

Endometrial injury for pregnancy following sexual intercourse or intrauterine insemination.

BACKGROUND: Intentional endometrial injury is 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 and is a common gynaecological procedure with established safety. However, it causes 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 intrauterine insemination (IUI), remains unclear. OBJECTIVES: To assess the effectiveness and safety of intentional endometrial injury performed in infertile women or couples attempting to conceive through sexual intercourse or intrauterine insemination (IUI). SEARCH METHODS: The Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, ISI Web of Knowledge, and clinical trial registries were searched from inception to 21 May 2020, as were conference abstracts and reference lists of relevant reviews and included studies. 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 ovarian stimulation (OS)) compared to no intervention, a mock intervention, or intentional endometrial injury performed at a different time. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Primary outcomes were live birth/ongoing pregnancy and pain experienced during the procedure. Due to high risk of bias associated with many of the studies, primary analyses of all review outcomes were restricted to studies at low risk of bias. Sensitivity analysis including all studies was then performed. MAIN RESULTS: We included 22 RCTs (3703 women). Most of these studies included women with unexplained infertility. Intentional endometrial injury versus either no intervention or a sham procedure The primary analysis was restricted to studies at low risk of bias, which left only one study included. We are uncertain whether endometrial injury has an effect on the probability of live birth, as only one study is included in the analysis and the confidence interval is wide (risk ratio (RR) 1.11, 95% confidence interval (CI) 0.78 to 1.59; 1 RCT, 210 participants). Evidence suggests that if the chance of live birth with no intervention/a sham procedure is assumed to be 34%, then the chance with endometrial injury would be 27% to 55%. When all studies were included in the sensitivity analysis, we were uncertain whether endometrial injury improves live birth/ongoing pregnancy, as the evidence was of very low quality (RR 1.71, 95% CI 1.32 to 2.21; 8 RCTs, 1522 participants; I² = 16%). Evidence suggests that if the chance of live birth/ongoing pregnancy with no intervention/a sham procedure is assumed to be 13%, then the chance with endometrial injury would be 17% to 28%. A narrative synthesis conducted for the other primary outcome of pain during the procedure included studies measuring pain on a zero-to-ten visual analogue scale (VAS) or grading pain as mild/moderate/severe, and showed that most often mild to moderate pain was reported (6 RCTs, 911 participants; very low-quality evidence). Timing of intentional endometrial injury Four trials compared endometrial injury performed in the cycle before IUI to that performed in the same cycle as IUI. None of these studies reported the primary outcomes of live birth/ongoing pregnancy and pain during the procedure. One study compared endometrial injury in the early follicular phase (EFP; Day 2 to 4) to endometrial injury in the late follicular phase (LFP; Day 7 to 9), both in the same cycle as IUI. The primary outcome live birth/ongoing pregnancy was not reported, but the study did report the other primary outcome of pain during the procedure assessed by a zero-to-ten VAS. The average pain score was 3.67 (standard deviation (SD) 0.7) when endometrial injury was performed in the EFP and 3.84 (SD 0.96) when endometrial injury was performed in the LFP. The mean difference was -0.17, suggesting that on average, women undergoing endometrial injury in the EFP scored 0.17 points lower on the VAS as compared to women undergoing endometrial injury in the LFP (95% CI -0.48 to 0.14; 1 RCT, 110 participants; very low-quality evidence). AUTHORS' CONCLUSIONS: Evidence is insufficient to show whether there is a difference in live birth/ongoing pregnancy between endometrial injury and no intervention/a sham procedure in women undergoing IUI or attempting to conceive via sexual intercourse. The pooled results should be interpreted with caution, as the evidence was of low to very low quality due to high risk of bias present in most included studies and an overall low level of precision. Furthermore, studies investigating the effect of timing of endometrial injury did not report the outcome live birth/ongoing pregnancy; therefore no conclusions could be drawn for this outcome. Further well-conducted RCTs that recruit large numbers of participants and minimise bias are required to confirm or refute these findings. Current evidence is insufficient to support routine use of endometrial injury in women undergoing IUI or attempting to conceive via sexual intercourse.

Luteal phase support for women trying to conceive by intrauterine insemination or sexual intercourse.

BACKGROUND: Ovulation induction may impact endometrial receptivity due to insufficient progesterone secretion. Low progesterone is associated with poor pregnancy outcomes. OBJECTIVES: To assess the effectiveness and safety of luteal phase support (LPS) in infertile women trying to conceive by intrauterine insemination or by sexual intercourse. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, LILACS, trial registries for ongoing trials, and reference lists of articles (from inception to 25 August 2021). SELECTION CRITERIA: Randomised controlled trials (RCTs) of LPS using progestogen, human chorionic gonadotropin (hCG), or gonadotropin-releasing hormone (GnRH) agonist supplementation in IUI or natural cycle. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were live birth rate/ongoing pregnancy rate (LBR/OPR) and miscarriage.  MAIN RESULTS: We included 25 RCTs (5111 participants). Most studies were at unclear or high risk of bias. We graded the certainty of evidence as very low to low. The main limitations of the evidence were poor reporting and imprecision. 1. Progesterone supplement versus placebo or no treatment  We are uncertain if vaginal progesterone increases LBR/OPR (risk ratio (RR) 1.10, 95% confidence interval (CI) 0.81 to 1.48; 7 RCTs; 1792 participants; low-certainty evidence) or decreases miscarriage per pregnancy compared to placebo or no treatment (RR 0.70, 95% CI 0.40 to 1.25; 5 RCTs; 261 participants). There were no data on LBR or miscarriage with oral stimulation. We are uncertain if progesterone increases LBR/OPR in women with gonadotropin stimulation (RR 1.24, 95% CI 0.80 to 1.92; 4 RCTs; 1054 participants; low-certainty evidence) and oral stimulation (clomiphene citrate or letrozole) (RR 0.97, 95% CI 0.58 to 1.64; 2 RCTs; 485 participants; low-certainty evidence). One study reported on OPR in women with gonadotropin plus oral stimulation; the evidence from this study was uncertain (RR 0.73, 95% CI 0.37 to 1.42; 1 RCT; 253 participants; low-certainty evidence). Given the low certainty of the evidence, it is unclear if progesterone reduces miscarriage per clinical pregnancy in any stimulation protocol (RR 0.68, 95% CI 0.24 to 1.91; 2 RCTs; 102 participants, with gonadotropin; RR 0.67, 95% CI 0.30 to 1.50; 2 RCTs; 123 participants, with gonadotropin plus oral stimulation; and RR 0.53, 95% CI 0.25 to 1.14; 2 RCTs; 119 participants, with oral stimulation). Low-certainty evidence suggests that progesterone in all types of ovarian stimulation may increase clinical pregnancy compared to placebo (RR 1.38, 95% CI 1.10 to 1.74; 7 RCTs; 1437 participants, with gonadotropin; RR 1.40, 95% CI 1.03 to 1.90; 4 RCTs; 733 participants, with gonadotropin plus oral stimulation (clomiphene citrate or letrozole); and RR 1.44, 95% CI 1.04 to 1.98; 6 RCTs; 1073 participants, with oral stimulation). 2. Progesterone supplementation regimen  We are uncertain if there is any difference between 300 mg and 600 mg of vaginal progesterone for OPR and multiple pregnancy (RR 1.58, 95% CI 0.81 to 3.09; 1 RCT; 200 participants; very low-certainty evidence; and RR 0.50, 95% CI 0.05 to 5.43; 1 RCT; 200 participants, very low-certainty evidence, respectively). No other outcomes were reported for this comparison. There were three different comparisons between progesterone regimens. For OPR, the evidence is very uncertain for intramuscular (IM) versus vaginal progesterone (RR 0.59, 95% CI 0.34 to 1.02; 1 RCT; 225 participants; very low-certainty evidence); we are uncertain if there is any difference between oral and vaginal progesterone (RR 1.25, 95% CI 0.70 to 2.22; 1 RCT; 150 participants; very low-certainty evidence) or between subcutaneous and vaginal progesterone (RR 1.05, 95% CI 0.54 to 2.05; 1 RCT; 246 participants; very low-certainty evidence). We are uncertain if IM or oral progesterone reduces miscarriage per clinical pregnancy compared to vaginal progesterone (RR 0.75, 95% CI 0.43 to 1.32; 1 RCT; 81 participants and RR 0.58, 95% CI 0.11 to 3.09; 1 RCT; 41 participants, respectively). Clinical pregnancy and multiple pregnancy were reported for all comparisons; the evidence for these outcomes was very uncertain. Only one RCT reported adverse effects. We are uncertain if IM route increases the risk of adverse effects when compared with the vaginal route (RR 9.25, 95% CI 2.21 to 38.78; 1 RCT; 225 participants; very low-certainty evidence). 3. GnRH agonist versus placebo or no treatment  No trials reported live birth. The evidence is very uncertain about the effect of GnRH agonist in ongoing pregnancy (RR 1.10, 95% CI 0.70 to 1.74; 1 RCT; 291 participants, very low-certainty evidence), miscarriage per clinical pregnancy (RR 0.73, 95% CI 0.26 to 2.10; 2 RCTs; 79 participants, very low-certainty evidence) and clinical pregnancy (RR 1.00, 95% CI 0.68 to 1.47; 2 RCTs; 340 participants; very low-certainty evidence), and multiple pregnancy (RR 0.28, 95% CI 0.11 to 0.70; 2 RCTs; 126 participants). 4. GnRH agonist versus vaginal progesterone  The evidence for the effect of GnRH agonist injection on clinical pregnancy is very uncertain (RR 1.00, 95% CI 0.51 to 1.95; 1 RCT; 242 participants). 5. HCG injection versus no treatment  The evidence for the effect of hCG injection on clinical pregnancy (RR 0.93, 95% CI 0.40 to 2.13; 1 RCT; 130 participants) and multiple pregnancy rates (RR 1.03, 95% CI 0.22 to 4.92; 1 RCT; 130 participants) is very uncertain. 6. Luteal support in natural cycle No study evaluated the effect of LPS in natural cycle. We could not perform sensitivity analyses, as there were no studies at low risk of selection bias and not at high risk in other domains. AUTHORS' CONCLUSIONS: We are uncertain if vaginal progesterone supplementation during luteal phase is associated with a higher live birth/ongoing pregnancy rate. Vaginal progesterone may increase clinical pregnancy rate; however, its effect on miscarriage rate and multiple pregnancy rate is uncertain. We are uncertain if IM progesterone improves ongoing pregnancy rates or decreases miscarriage rate when compared to vaginal progesterone. Regarding the other reported comparisons, neither oral progesterone nor any other medication appears to be associated with an improvement in pregnancy outcomes (very low-certainty evidence).

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.

The impact of adenomyosis on IVF outcomes: a prospective cohort study.

STUDY QUESTION: Does the presence of adenomyosis in women treated with IVF alter IVF outcomes? SUMMARY ANSWER: Adenomyosis does not significantly alter IVF outcomes when adjusted for confounding factors including maternal age and smoking status. WHAT IS KNOWN ALREADY: Studies evaluating adenomyosis and its impact on infertility, particularly when focusing on IVF, remain controversial. Many studies report that adenomyosis has a detrimental effect on IVF outcomes, however age is strongly related with both the prevalence of adenomyosis and worse reproductive outcomes. STUDY DESIGN SIZE DURATION: A prospective cohort study of women undergoing 4002 IVF cycles who had undergone a screening ultrasound assessing features of adenomyosis from 1 January 2016 to 31 March 2018 at a multi-site private fertility clinic. Of these women, 1228 fulfilled the inclusion criteria and commenced an IVF cycle, with a subset of 715 women undergoing an embryo transfer (ET). Women were defined as having adenomyosis if there was sonographic evidence of adenomyosis on ultrasound as per the Morphological Uterus Sonographic Assessment criteria, and were then compared to women without. PARTICIPANTS/MATERIALS SETTING METHODS: All women at a private multi-site IVF clinic who underwent a standardised ultrasound to identify features of adenomyosis and also commenced an IVF cycle were assessed for their outcomes. These included clinical pregnancy (defined as the presence of a gestational sac on ultrasound at 7 weeks' gestation), clinical pregnancy loss, number of cancelled cycles, number of useful embryos for transfer or freezing and live birth rates. As a secondary aim, initiated stimulation cycles and those that had an ET were analysed separately to determine when an effect of adenomyosis on IVF might occur: during stimulation or transfer. MAIN RESULTS AND THE ROLE OF CHANCE: When adjusting for confounders, women with and without sonographic features of adenomyosis had no significant differences in most of their IVF outcomes including live birth rates. LIMITATIONS REASONS FOR CAUTION: Adenomyosis had a detrimental impact on IVF outcomes prior to adjusting for confounding factors. No allowance was made for the possibility that confounding factors may merely reduce the effect size of adenomyosis on IVF outcomes. Second, despite a power calculation, the study was underpowered as not all fresh cycles led to an ET. WIDER IMPLICATIONS OF THE FINDINGS: This is one of the largest studies to evaluate adenomyosis and IVF outcomes, while also importantly adjusting for confounding factors. The results suggest that adenomyosis does not have the detrimental impact on IVF that has previously been suggested, possibly reducing the importance of screening for and treating this entity. STUDY FUNDING/COMPETING INTERESTS: The study received no external funding. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: ACTRN12617000796381.

Endometrial injury for pregnancy following sexual intercourse or intrauterine insemination.

BACKGROUND: Intentional endometrial injury is 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 and is a common gynaecological procedure with established safety. However, it causes 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 intrauterine insemination (IUI), remains unclear. OBJECTIVES: To assess the effectiveness and safety of intentional endometrial injury performed in infertile women or couples attempting to conceive through sexual intercourse or intrauterine insemination (IUI). SEARCH METHODS: The Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, ISI Web of Knowledge, and clinical trial registries were searched from inception to 21 May 2020, as were conference abstracts and reference lists of relevant reviews and included studies. 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 ovarian stimulation (OS)) 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: We used standard methodological procedures recommended by Cochrane. Primary outcomes were live birth/ongoing pregnancy and pain experienced during the procedure. Due to high risk of bias associated with many of the studies, primary analyses of all review outcomes were restricted to studies at low risk of bias. Sensitivity analysis including all studies was then performed. MAIN RESULTS: We included 23 RCTs (4035 women). Most of these studies included women with unexplained infertility. Intentional endometrial injury versus either no intervention or a sham procedure The primary analysis was restricted to studies at low risk of bias, which left only one study included. We are uncertain whether endometrial injury has an effect on the probability of live birth, as only one study is included in the analysis and the confidence interval is wide (risk ratio (RR) 1.11, 95% confidence interval (CI) 0.78 to 1.59; 1 RCT, 210 participants). Evidence suggests that if the chance of live birth with no intervention/a sham procedure is assumed to be 34%, then the chance with endometrial injury would be 27% to 55%. When all studies were included in the sensitivity analysis, we were uncertain whether endometrial injury improves live birth/ongoing pregnancy, as the evidence was of very low quality (RR 1.71, 95% CI 1.32 to 2.21; 8 RCTs, 1522 participants; I² = 16%). Evidence suggests that if the chance of live birth/ongoing pregnancy with no intervention/a sham procedure is assumed to be 13%, then the chance with endometrial injury would be 17% to 28%. A narrative synthesis conducted for the other primary outcome of pain during the procedure included studies measuring pain on a zero-to-ten visual analogue scale (VAS) or grading pain as mild/moderate/severe, and showed that most often mild to moderate pain was reported (6 RCTs, 911 participants; very low-quality evidence). Higher versus lower degree of intentional endometrial injury Evidence was insufficient to show whether there is a difference in ongoing pregnancy rates (RR 1.29, 95% CI 0.71 to 2.35; 1 RCT, 332 participants; low-quality evidence) between hysteroscopy with endometrial injury and hysteroscopy alone. Evidence suggests that if the chance of ongoing pregnancy with hysteroscopy alone is 10%, then the chance with hysteroscopy with endometrial injury would be 7% to 24%. This study did not report the primary outcomes of live birth and pain during the procedure. Timing of intentional endometrial injury Four trials compared endometrial injury performed in the cycle before IUI to that performed in the same cycle as IUI. None of these studies reported the primary outcomes of live birth/ongoing pregnancy and pain during the procedure. One study compared endometrial injury in the early follicular phase (EFP; Day 2 to 4) to endometrial injury in the late follicular phase (LFP; Day 7 to 9), both in the same cycle as IUI. The primary outcome live birth/ongoing pregnancy was not reported, but the study did report the other primary outcome of pain during the procedure assessed by a zero-to-ten VAS. The average pain score was 3.67 (standard deviation (SD) 0.7) when endometrial injury was performed in the EFP and 3.84 (SD 0.96) when endometrial injury was performed in the LFP. The mean difference was -0.17, suggesting that on average, women undergoing endometrial injury in the EFP scored 0.17 points lower on the VAS as compared to women undergoing endometrial injury in the LFP (95% CI -0.48 to 0.14; 1 RCT, 110 participants; very low-quality evidence). AUTHORS' CONCLUSIONS: Evidence is insufficient to show whether there is a difference in live birth/ongoing pregnancy between endometrial injury and no intervention/a sham procedure in women undergoing IUI or attempting to conceive via sexual intercourse. The pooled results should be interpreted with caution, as the evidence was of low to very low quality due to high risk of bias present in most included studies and an overall low level of precision. Furthermore, studies investigating the effect of timing of endometrial injury did not report the outcome live birth/ongoing pregnancy; therefore no conclusions could be drawn for this outcome. Further well-conducted RCTs that recruit large numbers of participants and minimise bias are required to confirm or refute these findings. Current evidence is insufficient to support routine use of endometrial injury in women undergoing IUI or attempting to conceive via sexual intercourse.

Conservative vs radical bowel surgery for endometriosis: A systematic analysis of complications.

BACKGROUND: Endometriosis of the bowel can be associated with significant morbidity. Surgery to remove it carries risks. Options include conservative shaving or discoid resection and more radical segmental bowel resection. AIMS: To determine if more conservative shaving or discoid bowel resection is associated with fewer risks than more radical segmental resection. MATERIAL AND METHODS: This study is a systematic review. We considered eligible any cohort, observational or randomised controlled trial (RCT) study of at least ten women per arm comparing conservative vs radical bowel surgery for endometriosis. We divided complications into two groups, major and minor. One additional article was added due to its significance in answering our study question as well as the high quality of the study design as an RCT. RESULTS: There were 3041 studies screened. Eleven studies were included (n = 1648). For major complications, the risk ratio for shaving and disc excision vs segmental resection is 0.31 (95% CI 0.21-0.46), while the risk difference is -0.25 (95% CI -0.41 to 0.10). For minor complications, the risk ratio is 0.63 (95% CI 0.36-1.09), while the risk difference is -0.03 (95% CI -0.12 to 0.05). CONCLUSIONS: Conservative shaving or discoid excision surgery is associated with reduced complications. Previous studies demonstrated a trend toward this finding, but suffered from relatively low participant numbers, increasing the risk of type one statistical error. Our results allow surgeons to make informed choices about potential complications when deciding how to approach bowel endometriosis. The results also allow patients to have more information about the risks. However, outcomes in the studies analysed are heterogenous and are from low-quality evidence.

Reference ranges for the left ventricle modified myocardial performance index, respective time periods, and atrioventricular peak velocities between 20 and 36 + 6 weeks of gestation.

Objective: To establish reference ranges for the fetal left ventricle (LV) modified myocardial performance index (Mod-MPI), respective time periods, and right and left atrioventricular peak velocities between 20 and 36 + 6 weeks of gestation.Methods: This cross-sectional study evaluated 360 low-risk singleton pregnancies between 20 and 36 + 6 weeks of gestation. The LV Mod-MPI was calculated as (isovolumetric contraction time + isovolumetric relaxation time)/ejection time. Polynomial regression was used to obtain the best-fit using Mod-MPI and atrioventricular peak velocity measurements and gestational age (GA) with adjustments using the coefficient of determination (R2). The intra- and interobserver reliability was evaluated using the concordance correlation coefficient (CCC).Results: LV Mod-MPI (R2 = 0.026, p = .002) and isovolumetric relaxation time (IRT) (R2 = 0.036, p < .001) significantly increased with advancing GA. Isovolumetric contraction time (ICT) and ejection time (ET) did not significantly change with GA. RV and LV E wave, A wave, and E/A ratio significantly increased with GA (p < .001). The mean of each parameter ranged as follows: LV Mod-MPI (0.44-0.47 s), IRT (0.041-0.045 s), ICT (0.032-0.034 s), ET (0.167-0.167 s), RV E (30.2-46.91 cm/s), RV A (47.1-60.7 cm/s), RV E/A (0.65-0.78 cm/s), LV E (27.0-41.4 cm/s), LV A (43.2-53.8 cm/s), and LV E/A (0.63-0.78 cm/s). Only LV A wave measurements demonstrated an intraobserver CCC >0.80. The remaining intra- and interobserver reproducibility parameters demonstrated lower CCC.Conclusions: Reference values were replicated for the fetal LV Mod-MPI and LV and RV transvalvular peak velocities between 20 and 36 + 6 weeks of gestation.

References Values of Fetal Heart Myocardial Volume by Three-Dimensional Ultrasound using Spatiotemporal Image Correlation and Virtual Organ Computer-Aided Analysis Methods and Their Applicability in Pregestational Diabetic Women.

OBJECTIVE: To determine reference values for myocardial volume of the fetal heart using three-dimensional ultrasound with spatiotemporal image correlation (STIC) and virtual organ computer-aided analysis (VOCAL) and to assess their applicability in women with pregestational diabetes. STUDY DESIGN: This retrospective cross-sectional study included 177 normal pregnant women with fetuses between 200/7 and 336/7 weeks of age. Fetal cardiac volumes were collected using the STIC method, and myocardial volume was obtained by subtraction of the intracavitary volumes using the VOCAL 30-degree method. Intra- and interobserver reproducibility values were determined using the concordance correlation coefficient (CCC). Sixteen women with pregestational diabetes mellitus were evaluated for validation. RESULTS: There was a strong correlation between fetal myocardial volume and gestational age (R 2 = 0.82). Intra- and interobserver reproducibility values were excellent and moderate, respectively, with CCCs of 0.99 and 0.83, respectively. There was no significant difference in mean fetal myocardial volume between normal pregnant women and those with pregestational diabetes (p = 0.64). CONCLUSION: Reference values for myocardial volume of the fetal heart were determined in normal pregnant women and were not statistically different from those in women with pregestational diabetes mellitus.

Tubal Flushing Treatment for Unexplained Infertility.

Tubal patency testing was initially introduced as a diagnostic test. However, it has been observed that some tubal patency tests also have a therapeutic effect. This therapeutic effect can be influenced by the contrast medium used during tubal flushing. In this review, we discuss current evidence associated with different methods for tubal flushing and their potential impact on reproductive outcomes in women with unexplained infertility. Furthermore, we discuss their diagnostic accuracy, safety, and cost-effectiveness.

Longitudinal vaginal septum: a proposed classification and surgical management.

OBJECTIVE: To demonstrate various types of longitudinal vaginal septa (LVS), their classification, and the surgical management of typical and unique morphologic conditions of LVS. DESIGN: Video presentation of clinical appearance and surgical techniques for treatment of LVS. SETTING: University hospital and two private. PATIENT(S): Representative cases from 121 consecutive women treated from 2013 to 2018 with LVS as a part of complex uterovaginal malformations or in isolated forms with [1] typical morphologic configuration of LVS, [2] rarer variants, or [3] specific anatomic restrictions. INTERVENTION(S): Resection of LVS performed as a main surgical procedure in cases with didelphys and bicornuate uterus in symptomatic women and as a part of corrective surgery of complete septate uterus. The three main nonsuturing techniques used were speculoscopy and septum excision using three different electrosurgical modalities; speculoscopy with laparoscopic devices; and vaginoscopy with hysteroscopic instruments. MAIN OUTCOME MEASURE(S): Clinical appearance and suggested classification, feasibility of surgery, and perioperative and anatomic results in a short follow-up period (3 months). RESULT(S): We identified distinct types of longitudinal vaginal septa. Considering clinical appearance, we suggest classification of LVS based on four main features: [2] completeness of vaginal division: partial and complete type; [2] the symmetricity: symmetric and asymmetric position (with dominant left and right side); [3] association with the cervix: merged and isolated forms; and [4] concomitant vaginal openings: normal, and narrow openings: vaginal stenosis and hymen persistent (Fig. 1). Vaginoscopic techniques by hysteroscope were successful in atraumatic treatment of women with substantial anatomic restrictions, and all of the presented techniques can be effectively used for typical LVS. However, vessel-sealing systems allow for bloodless surgery in contrast with other methods. This study was based on previously acquired data during large prospective study approved by the local ethics committee, and written informed consent to participate in the prospective study and permit publishing anonymous data regarding the medical images, videos of procedures, and results was obtained from all patients. CONCLUSION(S): A new classification of longitudinal vaginal septum allows better characterization compared with the currently available classification systems. Different surgical modalities are discussed with their respective advantages and disadvantages. Vaginoscopic incision using resectoscope is a reasonable alternative for women with an intact hymen and vaginal stenosis. The impact of vaginal septum resection on obstetric, reproductive, and sexual outcomes should be assessed in randomized controlled trials and large well-designed studies.

Reference ranges of filling time and systolic-to-diastolic time index of the left ventricle, right ventricle, and interventricular septum using both spectral and tissue Doppler of fetal heart between 20 and 36 + 6 weeks of gestation.

OBJECTIVE: The objective of this study is to determine the reference ranges for filling time (FT) and systolic-to-diastolic time index (SDI) of the left ventricle (LV) by using spectral Doppler, and FT' and SDI' of the LV, right ventricle, and interventricular septum (IVS) by using tissue Doppler of the fetal heart. STUDY DESIGN: This prospective and cross-sectional study included 360 low-risk singleton pregnancies between 20 and 36 + 6 weeks of gestation. The SDI/SDI' is the sum of the ejection time, isovolumic contraction time, and isovolumic relaxation time (IRT) divided by the FT. We measured FT/FT' from the beginning of the opening click of the E wave of the mitral valve to the closing click of the A wave of the mitral valve. We used regression analysis to obtain the best-fit model polynomial equation for the parameters. Additionally, we assessed intra- and inter-observer reproducibility by using concordance correlation coefficient (CCC). RESULTS: There was a weak correlation among FT LV (r = 0.31, p < 0.0001), SDI LV (r = -0.23, p < 0.0001), and gestational age (GA). Additionally, there was a very weak positive correlation among FT' RV (r = 0.09, p = 0.0001), FT' LV (r = 0.07, p < 0.0001), FT' IVS (r = 0,08, p < 0.0001), and GA. In contrast, there was a very weak negative correlation among SDI' LV (r=-0.09, p < 0.0001), SDI' IVS (r=-0.05, p < 0.0021), and GA. There was no significative correlation between SDI' RV (r=-0.06, p < 0.081) and GA. Poor/very poor intra- and inter-observer reliability was observed for all the parameters (CCC = 0.19-0.79), whereas moderate intra- and inter-observer agreement was observed for all parameters (CCC = 0.37-0.72). CONCLUSIONS: The reference ranges for FT and SDI were determined by using spectral and tissue Doppler of the fetal heart and showed a poor reproducibility.

Reference ranges for the fetal mitral, tricuspid, and interventricular septum annular plane systolic excursions (mitral annular plane systolic excursion, tricuspid annular plane systolic excursion, and septum annular plane systolic excursion) between 20 and 36 + 6 weeks of gestation.

Objectives This study aimed to establish reference ranges for fetal mitral, tricuspid, and interventricular septum annular plane systolic excursions (MAPSE, TAPSE, and SAPSE) in normal pregnant women between 20 and 36 + 6 weeks of gestation. Methods This prospective and cross-sectional study included 360 low-risk singleton pregnancies between 20 and 36 + 6 weeks of gestation. MAPSE, TAPSE, and SAPSE were measured by M-mode in real time in an apical or basal four-chamber view through placing the cursor at the atrioventricular junction, marked by the valve rings at the tricuspid, mitral, and basal septum, respectively. A regression analysis was done to determine the appropriate polynomial equation model for both measurements and standard deviation (SD) values in relation to gestational age (GA). The intra- and inter-observer reproducibility was evaluated using the concordance correlation coefficient (CCC) and limits of agreement (LoA). Results There was a significant positive correlation between MAPSE (r=0.705, p<0.0001), TAPSE (r=0.804, p<0.0001), and SAPSE (r=0.690, p<0.0001) and GA. The mean of each parameter ranged as follows: 2.87-5.56 mm, MAPSE; 3.98-8.07 mm, TAPSE; and 2.34-4.21 mm, SAPSE. Poor/moderate intra- and inter-observer reliability (CCC between 0.70 and 0.90) and poor/moderate agreement of all the tested parameters were evaluated (LoA between 10 and 50%). Conclusions Reference values were established for the fetal MAPSE, TAPSE, and SAPSE between 20 and 36 + 6 weeks of gestation in low-risk pregnant women. These parameters showed poor/moderate reproducibility.

Impact of type I and type II maternal diabetes mellitus on fetal cardiac function assessment parameters using spectral and tissue Doppler.

The aim of this study was to evaluate the impact of pregestational diabetes mellitus (DM) on fetal cardiac function two-dimensional parameters using spectral and tissue Doppler. Pregnant women between 20 and 36 + 6 weeks gestation were divided into three groups: controls, type I DM, and type II DM. The right ventricle (RV) and left ventricle (LV) annular velocity peaks were measured using spectral (E, A) and tissue (E', A', S') Doppler. The myocardial performance index was calculated as (isovolumetric contraction time [ICT] + isovolumetric relaxation time [IRT])/ejection time using tissue (MPI') and the spectral Doppler (MPI). A general linear model, with fetal heart rate as a covariant, was used to evaluate the effect of DM on the fetal heart function assessment parameters. To assess the association of type I and II DM with adverse perinatal outcomes, Fisher's exact test was used. A receiver operating characteristic curve was used to determine the best cutoff for fetal cardiac function assessment parameters to identify the neonatal composite outcomes. The sample comprised 179 pregnant women. DM had significant effect on RV and LV A peak velocities (p = 0.026 and p = 0.011, respectively). LV ICT (p < 0.001) and LV MPI (p < 0.001) were significantly affected by maternal DM. Fetuses from pregnant women with type II DM showed significantly higher LV MPI (0.492 vs. 0.459, p = 0.006) and RV S' (7.2 vs. 6.44 cm/s, p = 0.024) than controls. Fetuses from type I DM pregnant women showed increase in cardiac parameters that evaluated the LV and RV diastolic function (LV IRT' p < 0.001 and RV MPI' p = 0.044). Type I and II DM were associated with adverse perinatal outcomes: neonatal intensive care unit stay (p < 0.0001), macrosomia (p < 0.0001), hyperbilirubinemia (p < 0.0001), and hypoglycemia (p < 0.0001). The LV MPI' showed significant but moderate sensitivity in identifying the composite neonatal outcomes (AUC: 0.709, 95% CI 0.629-0.780, p < 0.001). Tissue Doppler and MPI parameters can be useful to detect subclinical cardiac dysfunction in the fetal heart of pregestational DM pregnant women.

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.

Reference ranges for left, right and interventricular septum indices at 20 to 36+6 weeks of gestation derived using spectral myocardial tissue Doppler on Voluson ultrasound machines.

AIM: To establish reference range values for peak myocardial tissue Doppler velocity (MTD) and myocardial performance index (MPI) of the left ventricle (LV), the right ventricle (RV), and the interventricular septum (IVS) at 20 to 36+6 weeks of gestation using spectral tissue Doppler. MATERIAL AND METHODS: This cross-sectional study was conducted among 360 lowrisk singleton pregnancies. MTD during systole (S'), and early (E') and late diastole (A'), and MPI' were assessed by placing sample volume at the basal segment of the LV free wall, the RV free wall, and the IVS, respectively. Polynomial regression was used to obtain the best-fit curves for MTD and MPI' measurements as a function of gestational age (GA), and adjustments were made using the determination coefficient (R2). Intra- and inter-observer reproducibility was evaluated using the concordance correlation coefficient (CCC). RESULTS: All MTD velocities (cm/s) progressively increased with advancing GA (p<0.0001). Mean LV MTD values were 4.19 to 6.86 for S', 3.52 to 7.22 for E', and 6.85 to 9.19 for A'; mean RV MTD were 4.85 to 7.97 for S', 4.49 to 8.66 for E', and 8.44 to 11.20 for A'; and mean IVS MTD values were 3.75 to 5.78 for S', 3.34 to 5.79 for E', and 5.88 to 7.98 for A'. LV MPI', RV MPI', and IVS MPI' did not significantly change with advancing GA. The CCC values for MTD were predominantly greater than 0.70, while those for MPI' were <0.70. CONCLUSIONS: Reference values for the fetal MTD and MPI' of RV, LV and IVS using tissue Doppler between 20 and 36+6 weeks of gestation were described.