Intra-uterine insemination for unexplained subfertility.

BACKGROUND: Intra-uterine insemination (IUI) is a widely-used fertility treatment for couples with unexplained subfertility. Although IUI is less invasive and less expensive than in vitro fertilisation (IVF), the safety of IUI in combination with ovarian hyperstimulation (OH) is debated. The main concern about IUI treatment with OH is the increase in multiple pregnancy rates. OBJECTIVES: To determine whether, for couples with unexplained subfertility, the live birth rate is improved following IUI treatment with or without OH compared to timed intercourse (TI) or expectant management with or without OH, or following IUI treatment with OH compared to IUI in a natural cycle. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers up to 17 October 2019, together with reference checking and contact with study authors for missing or unpublished data. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing IUI with TI or expectant management, both in stimulated or natural cycles, or IUI in stimulated cycles with IUI in natural cycles in couples with unexplained subfertility. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, quality assessment and data extraction. Primary review outcomes were live birth rate and multiple pregnancy rate. MAIN RESULTS: We include 15 trials with 2068 women. The evidence was of very low to moderate quality. The main limitation was very serious imprecision. IUI in a natural cycle versus timed intercourse or expectant management in a natural cycle It is uncertain whether treatment with IUI in a natural cycle improves live birth rate compared to treatment with expectant management in a natural cycle (odds ratio (OR) 1.60, 95% confidence interval (CI) 0.92 to 2.78; 1 RCT, 334 women; low-quality evidence). If we assume the chance of a live birth with expectant management in a natural cycle to be 16%, that of IUI in a natural cycle would be between 15% and 34%. It is uncertain whether treatment with IUI in a natural cycle reduces multiple pregnancy rates compared to control (OR 0.50, 95% CI 0.04 to 5.53; 1 RCT, 334 women; low-quality evidence). IUI in a stimulated cycle versus timed intercourse or expectant management in a stimulated cycle It is uncertain whether treatment with IUI in a stimulated cycle improves live birth rates compared to treatment with TI in a stimulated cycle (OR 1.59, 95% CI 0.88 to 2.88; 2 RCTs, 208 women; I2 = 72%; low-quality evidence). If we assume the chance of achieving a live birth with TI in a stimulated cycle was 26%, the chance with IUI in a stimulated cycle would be between 23% and 50%. It is uncertain whether treatment with IUI in a stimulated cycle reduces multiple pregnancy rates compared to control (OR 1.46, 95% CI 0.55 to 3.87; 4 RCTs, 316 women; I2 = 0%; low-quality evidence). IUI in a stimulated cycle versus timed intercourse or expectant management in a natural cycle In couples with a low prediction score of natural conception, treatment with IUI combined with clomiphene citrate or letrozole probably results in a higher live birth rate compared to treatment with expectant management in a natural cycle (OR 4.48, 95% CI 2.00 to 10.01; 1 RCT; 201 women; moderate-quality evidence). If we assume the chance of a live birth with expectant management in a natural cycle was 9%, the chance of a live birth with IUI in a stimulated cycle would be between 17% and 50%. It is uncertain whether treatment with IUI in a stimulated cycle results in a lower multiple pregnancy rate compared to control (OR 3.01, 95% CI 0.47 to 19.28; 2 RCTs, 454 women; I2 = 0%; low-quality evidence). IUI in a natural cycle versus timed intercourse or expectant management in a stimulated cycle Treatment with IUI in a natural cycle probably results in a higher cumulative live birth rate compared to treatment with expectant management in a stimulated cycle (OR 1.95, 95% CI 1.10 to 3.44; 1 RCT, 342 women: moderate-quality evidence). If we assume the chance of a live birth with expectant management in a stimulated cycle was 13%, the chance of a live birth with IUI in a natural cycle would be between 14% and 34%. It is uncertain whether treatment with IUI in a natural cycle results in a lower multiple pregnancy rate compared to control (OR 1.05, 95% CI 0.07 to 16.90; 1 RCT, 342 women; low-quality evidence). IUI in a stimulated cycle versus IUI in a natural cycle Treatment with IUI in a stimulated cycle may result in a higher cumulative live birth rate compared to treatment with IUI in a natural cycle (OR 2.07, 95% CI 1.22 to 3.50; 4 RCTs, 396 women; I2 = 0%; low-quality evidence). If we assume the chance of a live birth with IUI in a natural cycle was 14%, the chance of a live birth with IUI in a stimulated cycle would be between 17% and 36%. It is uncertain whether treatment with IUI in a stimulated cycle results in a higher multiple pregnancy rate compared to control (OR 3.00, 95% CI 0.11 to 78.27; 2 RCTs, 65 women; low-quality evidence). AUTHORS' CONCLUSIONS: Due to insufficient data, it is uncertain whether treatment with IUI with or without OH compared to timed intercourse or expectant management with or without OH improves cumulative live birth rates with acceptable multiple pregnancy rates in couples with unexplained subfertility. However, treatment with IUI with OH probably results in a higher cumulative live birth rate compared to expectant management without OH in couples with a low prediction score of natural conception. Similarly, treatment with IUI in a natural cycle probably results in a higher cumulative live birth rate compared to treatment with timed intercourse with OH. Treatment with IUI in a stimulated cycle may result in a higher cumulative live birth rate compared to treatment with IUI in a natural cycle.

Cycle regimens for frozen-thawed embryo transfer.

BACKGROUND: Among subfertile couples undergoing assisted reproductive technology (ART), pregnancy rates following frozen-thawed embryo transfer (FET) treatment cycles have historically been found to be lower than following embryo transfer undertaken two to five days following oocyte retrieval. Nevertheless, FET increases the cumulative pregnancy rate, reduces cost, is relatively simple to undertake and can be accomplished in a shorter time period than repeated in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles with fresh embryo transfer. FET is performed using different cycle regimens: spontaneous ovulatory (natural) cycles; cycles in which the endometrium is artificially prepared by oestrogen and progesterone hormones, commonly known as hormone therapy (HT) FET cycles; and cycles in which ovulation is induced by drugs (ovulation induction FET cycles). HT can be used with or without a gonadotrophin releasing hormone agonist (GnRHa). This is an update of a Cochrane review; the first version was published in 2008. OBJECTIVES: To compare the effectiveness and safety of natural cycle FET, HT cycle FET and ovulation induction cycle FET, and compare subtypes of these regimens. SEARCH METHODS: On 13 December 2016 we searched databases including Cochrane Gynaecology and Fertility's Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL. Other search sources were trials registers and reference lists of included studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing the various cycle regimens and different methods used to prepare the endometrium during FET. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Our primary outcomes were live birth rates and miscarriage. MAIN RESULTS: We included 18 RCTs comparing different cycle regimens for FET in 3815 women. The quality of the evidence was low or very low. The main limitations were failure to report important clinical outcomes, poor reporting of study methods and imprecision due to low event rates. We found no data specific to non-ovulatory women. 1. Natural cycle FET comparisons Natural cycle FET versus HT FETNo study reported live birth rates, miscarriage or ongoing pregnancy.There was no evidence of a difference in multiple pregnancy rates between women in natural cycles and those in HT FET cycle (odds ratio (OR) 2.48, 95% confidence interval (CI) 0.09 to 68.14, 1 RCT, n = 21, very low-quality evidence). Natural cycle FET versus HT plus GnRHa suppressionThere was no evidence of a difference in rates of live birth (OR 0.77, 95% CI 0.39 to 1.53, 1 RCT, n = 159, low-quality evidence) or multiple pregnancy (OR 0.58, 95% CI 0.13 to 2.50, 1 RCT, n = 159, low-quality evidence) between women who had natural cycle FET and those who had HT FET cycles with GnRHa suppression. No study reported miscarriage or ongoing pregnancy. Natural cycle FET versus modified natural cycle FET (human chorionic gonadotrophin (HCG) trigger)There was no evidence of a difference in rates of live birth (OR 0.55, 95% CI 0.16 to 1.93, 1 RCT, n = 60, very low-quality evidence) or miscarriage (OR 0.20, 95% CI 0.01 to 4.13, 1 RCT, n = 168, very low-quality evidence) between women in natural cycles and women in natural cycles with HCG trigger. However, very low-quality evidence suggested that women in natural cycles (without HCG trigger) may have higher ongoing pregnancy rates (OR 2.44, 95% CI 1.03 to 5.76, 1 RCT, n = 168). There were no data on multiple pregnancy. 2. Modified natural cycle FET comparisons Modified natural cycle FET (HCG trigger) versus HT FETThere was no evidence of a difference in rates of live birth (OR 1.34, 95% CI 0.88 to 2.05, 1 RCT, n = 959, low-quality evidence) or ongoing pregnancy (OR 1.21, 95% CI 0.80 to 1.83, 1 RCT, n = 959, low-quality evidence) between women in modified natural cycles and those who received HT. There were no data on miscarriage or multiple pregnancy. Modified natural cycle FET (HCG trigger) versus HT plus GnRHa suppressionThere was no evidence of a difference between the two groups in rates of live birth (OR 1.11, 95% CI 0.66 to 1.87, 1 RCT, n = 236, low-quality evidence) or miscarriage (OR 0.74, 95% CI 0.25 to 2.19, 1 RCT, n = 236, low-quality evidence) rates. There were no data on ongoing pregnancy or multiple pregnancy. 3. HT FET comparisons HT FET versus HT plus GnRHa suppressionHT alone was associated with a lower live birth rate than HT with GnRHa suppression (OR 0.10, 95% CI 0.04 to 0.30, 1 RCT, n = 75, low-quality evidence). There was no evidence of a difference between the groups in either miscarriage (OR 0.64, 95% CI 0.37 to 1.12, 6 RCTs, n = 991, I2 = 0%, low-quality evidence) or ongoing pregnancy (OR 1.72, 95% CI 0.61 to 4.85, 1 RCT, n = 106, very low-quality evidence).There were no data on multiple pregnancy. 4. Comparison of subtypes of ovulation induction FET Human menopausal gonadotrophin(HMG) versus clomiphene plus HMG HMG alone was associated with a higher live birth rate than clomiphene combined with HMG (OR 2.49, 95% CI 1.07 to 5.80, 1 RCT, n = 209, very low-quality evidence). There was no evidence of a difference between the groups in either miscarriage (OR 1.33, 95% CI 0.35 to 5.09,1 RCT, n = 209, very low-quality evidence) or multiple pregnancy (OR 1.41, 95% CI 0.31 to 6.48, 1 RCT, n = 209, very low-quality evidence).There were no data on ongoing pregnancy. AUTHORS' CONCLUSIONS: This review did not find sufficient evidence to support the use of one cycle regimen in preference to another in preparation for FET in subfertile women with regular ovulatory cycles. The most common modalities for FET are natural cycle with or without HCG trigger or endometrial preparation with HT, with or without GnRHa suppression. We identified only four direct comparisons of these two modalities and there was insufficient evidence to support the use of either one in preference to the other.

Antibiotic prophylaxis for elective hysterectomy.

BACKGROUND: Elective hysterectomy is commonly performed for benign gynaecological conditions. Hysterectomy can be performed abdominally, laparoscopically, or vaginally, with or without laparoscopic assistance. Antibiotic prophylaxis consists of administration of antibiotics to reduce the rate of postoperative infection, which otherwise affects 40%-50% of women after vaginal hysterectomy, and more than 20% after abdominal hysterectomy. No Cochrane review has systematically assessed evidence on this topic. OBJECTIVES: To determine the effectiveness and safety of antibiotic prophylaxis in women undergoing elective hysterectomy. SEARCH METHODS: We searched electronic databases to November 2016 (including the Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Studies (CRSO), MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), as well as clinical trials registers, conference abstracts, and reference lists of relevant articles. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing use of antibiotics versus placebo or other antibiotics as prophylaxis in women undergoing elective hysterectomy. DATA COLLECTION AND ANALYSIS: We used Cochrane standard methodological procedures. MAIN RESULTS: We included in this review 37 RCTs, which performed 20 comparisons of various antibiotics versus placebo and versus one another (6079 women). The quality of the evidence ranged from very low to moderate. The main limitations of study findings were risk of bias due to poor reporting of methods, imprecision due to small samples and low event rates, and inadequate reporting of adverse effects. Any antibiotic versus placebo Vaginal hysterectomyModerate-quality evidence shows that women who received antibiotic prophylaxis had fewer total postoperative infections (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.19 to 0.40; five RCTs, N = 610; I2 = 85%), less urinary tract infection (UTI) (RR 0.58, 95% CI 0.43 to 0.77; eight RCTs, N = 1790; I2 = 44%), fewer pelvic infections (RR 0.28, 95% CI 0.20 to 0.39; 11 RCTs, N = 2010; I2 = 57%), and fewer postoperative fevers (RR 0.43, 95% CI 0.34 to 0.54; nine RCTs, N = 1879; I2 = 48%) than women who did not receive such prophylaxis. This suggests that antibiotic prophylaxis reduces the average risk of postoperative infection from about 34% to 7% to 14%. Whether this treatment has led to differences in rates of other serious infection remains unclear (RR 0.20, 95% CI 0.01 to 4.10; one RCT, N = 146; very low-quality evidence).Data were insufficient for comparison of adverse effects. Abdominal hysterectomyWomen who received antibiotic prophylaxis of any class had fewer total postoperative infections (RR 0.16, 95% CI 0.06 to 0.38; one RCT, N = 345; low-quality evidence), abdominal wound infections (RR 0.64, 95% CI 0.45 to 0.92; 11 RCTs, N = 2434; I2 = 0%; moderate-quality evidence), UTIs (RR 0.39, 95% CI 0.29 to 0.51; 11 RCTs, N = 2547; I2 = 26%; moderate-quality evidence), pelvic infections (RR 0.50, 95% CI 0.35 to 0.71; 11 RCTs, N = 1883; I2 = 11%; moderate-quality evidence), and postoperative fevers (RR 0.60, 95% CI 0.51 to 0.70; 11 RCTs, N = 2581; I2 = 51%; moderate-quality evidence) than women who did not receive prophylaxis, suggesting that antibiotic prophylaxis reduces the average risk of postoperative infection from about 16% to 1% to 6%. Whether this treatment has led to differences in rates of other serious infection remains unclear (RR 0.44, 95% CI 0.12 to 1.69; two RCTs, N = 476; I2 = 29%; very low-quality evidence).It is unclear whether rates of adverse effects differed between groups (RR 1.80, 95% CI 0.62 to 5.18; two RCTs, N = 430; I2 = 0%; very low-quality evidence). Head-to-head comparisons between antibiotics Vaginal hysterectomyWe identified four comparisons: cephalosporin versus penicillin (two RCTs, N = 470), cephalosporin versus tetracycline (one RCT, N = 51), antiprotozoal versus lincosamide (one RCT, N = 80), and cephalosporin versus antiprotozoal (one RCT, N = 78). Data show no evidence of differences between groups for any of the primary outcomes, except that fewer cases of total postoperative infection and postoperative fever were reported in women who received cephalosporin than in those who received antiprotozoal.Only one comparison (cephalosporin vs penicillin; two RCTs, N = 451) yielded data on adverse effects and showed no differences between groups. Abdominal hysterectomyWe identified only one comparison: cephalosporin versus penicillin (N = 220). Data show no evidence of differences between groups for any of the primary outcomes. Adverse effects were not reported. Combined antibiotics versus single antibiotics Vaginal hysterectomyWe identified three comparisons: cephalosporin plus antiprotozoal versus cephalosporin (one RCT, N = 78), cephalosporin plus antiprotozoal versus antiprotozoal (one RCT, N = 78), and penicillin plus antiprotozoal versus penicillin (one RCT, N = 230). Data were unavailable for most outcomes, including adverse effects. We found no evidence of differences between groups, except that fewer women receiving cephalosporin with antiprotozoal received a diagnosis of total postoperative infection, UTI, or postoperative fever compared with women receiving antiprotozoal. Abdominal hysterectomyWe identified one comparison (penicillin plus antiprotozoal vs penicillin only; one RCT, N = 230). Whether differences between groups occurred was unclear. Adverse effects were not reported. Comparison of cephalosporins in different regimensSingle small trials addressed dose comparisons and provided no data for most outcomes, including adverse effects. Whether differences between groups occurred was unclear. No trials compared route of administration.The quality of evidence for all head-to-head and dose comparisons was very low owing to very serious imprecision and serious risk of bias related to poor reporting of methods. AUTHORS' CONCLUSIONS: Antibiotic prophylaxis appears to be effective in preventing postoperative infection in women undergoing elective vaginal or abdominal hysterectomy, regardless of the dose regimen. However, evidence is insufficient to show whether use of prophylactic antibiotics influences rates of adverse effects. Similarly, evidence is insufficient to show which (if any) individual antibiotic, dose regimen, or route of administration is safest and most effective. The most recent studies included in this review were 14 years old at the time of our search. Thus findings from included studies may not reflect current practice in perioperative and postoperative care and may not show locoregional antimicrobial resistance patterns.

Oral contraceptive pill, progestogen or oestrogen pretreatment for ovarian stimulation protocols for women undergoing assisted reproductive techniques.

BACKGROUND: Among subfertile women undergoing assisted reproductive technology (ART), hormone pills given before ovarian stimulation may improve outcomes. OBJECTIVES: To determine whether pretreatment with the combined oral contraceptive pill (COCP) or with a progestogen or oestrogen alone in ovarian stimulation protocols affects outcomes in subfertile couples undergoing ART. SEARCH METHODS: We searched the following databases from inception to January 2017: Cochrane Gynaecology and Fertility Group Specialised Register, The Cochrane Central Register Studies Online, MEDLINE, Embase, CINAHL and PsycINFO. We also searched the reference lists of relevant articles and registers of ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) of hormonal pretreatment in women undergoing ART. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcomes were live birth or ongoing pregnancy and pregnancy loss. MAIN RESULTS: We included 29 RCTs (4701 women) of pretreatment with COCPs, progestogens or oestrogens versus no pretreatment or alternative pretreatments, in gonadotrophin-releasing hormone (GnRH) agonist or antagonist cycles. Overall, evidence quality ranged from very low to moderate. The main limitations were risk of bias and imprecision. Most studies did not describe their methods in adequate detail. Combined oral contraceptive pill versus no pretreatmentWith antagonist cycles in both groups the rate of live birth or ongoing pregnancy was lower in the pretreatment group (OR 0.74, 95% CI 0.58 to 0.95; 6 RCTs; 1335 women; I2 = 0%; moderate quality evidence). There was insufficient evidence to determine whether the groups differed in rates of pregnancy loss (OR 1.36, 95% CI 0.82 to 2.26; 5 RCTs; 868 women; I2 = 0%; moderate quality evidence), multiple pregnancy (OR 2.21, 95% CI 0.53 to 9.26; 2 RCTs; 125 women; I2 = 0%; low quality evidence), ovarian hyperstimulation syndrome (OHSS; OR 0.98, 95% CI 0.28 to 3.40; 2 RCTs; 642 women; I2 = 0%, low quality evidence), or ovarian cyst formation (OR 0.47, 95% CI 0.08 to 2.75; 1 RCT; 64 women; very low quality evidence).In COCP plus antagonist cycles versus no pretreatment in agonist cycles, there was insufficient evidence to determine whether the groups differed in rates of live birth or ongoing pregnancy (OR 0.89, 95% CI 0.64 to 1.25; 4 RCTs; 724 women; I2 = 0%; moderate quality evidence), multiple pregnancy (OR 1.36, 95% CI 0.85 to 2.19; 4 RCTs; 546 women; I2 = 0%; moderate quality evidence), or OHSS (OR 0.63, 95% CI 0.20 to 1.96; 2 RCTs; 290 women, I2 = 0%), but there were fewer pregnancy losses in the pretreatment group (OR 0.40, 95% CI 0.22 to 0.72; 5 RCTs; 780 women; I2 = 0%; moderate quality evidence). There were no data suitable for analysis on ovarian cyst formation.One small study comparing COCP versus no pretreatment in agonist cycles showed no clear difference between the groups for any of the reported outcomes. Progestogen versus no pretreatmentAll studies used the same protocol (antagonist, agonist or gonadotrophins) in both groups. There was insufficient evidence to determine any differences in rates of live birth or ongoing pregnancy (agonist: OR 1.35, 95% CI 0.69 to 2.65; 2 RCTs; 222 women; I2 = 24%; low quality evidence; antagonist: OR 0.67, 95% CI 0.18 to 2.54; 1 RCT; 47 women; low quality evidence; gonadotrophins: OR 0.63, 95% CI 0.09 to 4.23; 1 RCT; 42 women; very low quality evidence), pregnancy loss (agonist: OR 2.26, 95% CI 0.67 to 7.55; 2 RCTs; 222 women; I2 = 0%; low quality evidence; antagonist: OR 0.36, 95% CI 0.06 to 2.09; 1 RCT; 47 women; low quality evidence; gonadotrophins: OR 1.00, 95% CI 0.06 to 17.12; 1 RCT; 42 women; very low quality evidence) or multiple pregnancy (agonist: no data available; antagonist: OR 1.05, 95% CI 0.06 to 17.76; 1 RCT; 47 women; low quality evidence; gonadotrophins: no data available). Three studies, all using agonist cycles, reported ovarian cyst formation: rates were lower in the pretreatment group (OR 0.16, 95% CI 0.08 to 0.32; 374 women; I2 = 1%; moderate quality evidence). There were no data on OHSS. Oestrogen versus no pretreatmentIn antagonist or agonist cycles, there was insufficient evidence to determine whether the groups differed in rates of live birth or ongoing pregnancy (antagonist versus antagonist: OR 0.79, 95% CI 0.53 to 1.17; 2 RCTs; 502 women; I2 = 0%; low quality evidence; antagonist versus agonist: OR 0.88, 95% CI 0.51 to 1.50; 2 RCTs; 242 women; I2 = 0%; very low quality evidence), pregnancy loss (antagonist versus antagonist: OR 0.16, 95% CI 0.02 to 1.47; 1 RCT; 49 women; very low quality evidence; antagonist versus agonist: OR 1.59, 95% CI 0.62 to 4.06; 1 RCT; 220 women; very low quality evidence), multiple pregnancy (antagonist versus antagonist: no data available; antagonist versus agonist: OR 2.24, 95% CI 0.09 to 53.59; 1 RCT; 22 women; very low quality evidence) or OHSS (antagonist versus antagonist: no data available; antagonist versus agonist: OR 1.54, 95% CI 0.25 to 9.42; 1 RCT; 220 women). Ovarian cyst formation was not reported. Head-to-head comparisonsCOCP was compared with progestogen (1 RCT, 44 women), and with oestrogen (2 RCTs, 146 women), and progestogen was compared with oestrogen (1 RCT, 48 women), with an antagonist cycle in both groups. COCP in an agonist cycle was compared with oestrogen in an antagonist cycle (1 RCT, 25 women). Data were scant but there was no clear evidence that any of the groups differed in rates of live birth or ongoing pregnancy, pregnancy loss or other adverse events. AUTHORS' CONCLUSIONS: Among women undergoing ovarian stimulation in antagonist protocols, COCP pretreatment was associated with a lower rate of live birth or ongoing pregnancy than no pretreatment. There was insufficient evidence to determine whether rates of live birth or ongoing pregnancy were influenced by pretreatment with progestogens or oestrogens, or by COCP pretreatment using other stimulation protocols. Findings on adverse events were inconclusive, except that progesterone pretreatment may reduce the risk of ovarian cysts in agonist cycles, and COCP in antagonist cycles may reduce the risk of pregnancy loss compared with no pretreatment in agonist cycles.

Recombinant luteinizing hormone (rLH) and recombinant follicle stimulating hormone (rFSH) for ovarian stimulation in IVF/ICSI cycles.

BACKGROUND: One of the various ovarian stimulation regimens used for in-vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles is the use of recombinant follicle-stimulating hormone (rFSH) in combination with a gonadotrophin-releasing hormone (GnRH) analogue. GnRH analogues prevent premature luteinizing hormone (LH) surges. Since they deprive the growing follicles of LH, the question arises as to whether supplementation with recombinant LH (rLH) would increase live birth rates. This is an updated Cochrane Review; the original version was published in 2007. OBJECTIVES: To compare the effectiveness and safety of recombinant luteinizing hormone (rLH) combined with recombinant follicle-stimulating hormone (rFSH) for ovarian stimulation compared to rFSH alone in women undergoing in-vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI). SEARCH METHODS: For this update we searched the following databases in June 2016: the Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and ongoing trials registers, and checked the references of retrieved articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing rLH combined with rFSH versus rFSH alone in IVF/ISCI cycles. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias, and extracted data. We combined data to calculate odds ratios (ORs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I2 statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. Our primary outcomes were live birth rate and incidence of ovarian hyperstimulation syndrome (OHSS). Secondary outcomes included ongoing pregnancy rate, miscarriage rate and cancellation rates (for poor response or imminent OHSS). MAIN RESULTS: We included 36 RCTs (8125 women). The quality of the evidence ranged from very low to moderate. The main limitations were risk of bias (associated with poor reporting of methods) and imprecision.Live birth rates: There was insufficient evidence to determine whether there was a difference between rLH combined with rFSH versus rFSH alone in live birth rates (OR 1.32, 95% CI 0.85 to 2.06; n = 499; studies = 4; I2 = 63%, very low-quality evidence). The evidence suggests that if the live birth rate following treatment with rFSH alone is 17% it will be between 15% and 30% using rLH combined with rFSH.OHSS: There may be little or no difference between rLH combined with rFSH versus rFSH alone in OHSS rates (OR 0.38, 95% CI 0.14 to 1.01; n = 2178; studies = 6; I2 = 10%, low-quality evidence). The evidence suggests that if the rate of OHSS following treatment with rFSH alone is 1%, it will be between 0% and 1% using rLH combined with rFSH.Ongoing pregnancy rate: The use of rLH combined with rFSH probably improves ongoing pregnancy rates, compared to rFSH alone (OR 1.20, 95% CI 1.01 to 1.42; participants = 3129; studies = 19; I2 = 2%, moderate-quality evidence). The evidence suggests that if the ongoing pregnancy rate following treatment with rFSH alone is 21%, it will be between 21% and 27% using rLH combined with rFSH.Miscarriage rate: The use of rLH combined with rFSH probably makes little or no difference to miscarriage rates, compared to rFSH alone (OR 0.93, 95% CI 0.63 to 1.36; n = 1711; studies = 13; I2 = 0%, moderate-quality evidence). The evidence suggests that if the miscarriage rate following treatment with rFSH alone is 7%, the miscarriage rate following treatment with rLH combined with rFSH will be between 4% and 9%.Cancellation rates: There may be little or no difference between rLH combined with rFSH versus rFSH alone in rates of cancellation due to low response (OR 0.77, 95% CI 0.54 to 1.10; n = 2251; studies = 11; I2 = 16%, low quality evidence). The evidence suggests that if the risk of cancellation due to low response following treatment with rFSH alone is 7%, it will be between 4% and 7% using rLH combined with rFSH.We are uncertain whether use of rLH combined with rFSH improves rates of cancellation due to imminent OHSS compared to rFSH alone. Use of a fixed effect model suggested a benefit in the combination group (OR 0.60, 95% CI 0.40 to 0.89; n = 2976; studies = 8; I2 = 60%, very low quality evidence) but use of a random effects model did not support the conclusion that there was a difference between the groups (OR 0.82, 95% CI 0.34 to 1.97). AUTHORS' CONCLUSIONS: We found no clear evidence of a difference between rLH combined with rFSH and rFSH alone in rates of live birth or OHSS. The evidence for these comparisons was of very low-quality for live birth and low quality for OHSS. We found moderate quality evidence that the use of rLH combined with rFSH may lead to more ongoing pregnancies than rFSH alone. There was also moderate-quality evidence suggesting little or no difference between the groups in rates of miscarriage. There was no clear evidence of a difference between the groups in rates of cancellation due to low response or imminent OHSS, but the evidence for these outcomes was of low or very low quality.We conclude that the evidence is insufficient to encourage or discourage stimulation regimens that include rLH combined with rFSH in IVF/ICSI cycles.

Local oestrogen for vaginal atrophy in postmenopausal women.

BACKGROUND: Vaginal atrophy is a frequent complaint of postmenopausal women; symptoms include vaginal dryness, itching, discomfort and painful intercourse. Systemic treatment for these symptoms in the form of oral hormone replacement therapy is not always necessary. An alternative choice is oestrogenic preparations administered vaginally (in the form of creams, pessaries, tablets and the oestradiol-releasing ring). This is an update of a Chochrane systematic review; the original version was first published in October 2006. OBJECTIVES: The objective of this review was to compare the efficacy and safety of intra-vaginal oestrogenic preparations in relieving the symptoms of vaginal atrophy in postmenopausal women. SEARCH METHODS: We searched the following databases and trials registers to April 2016: Cochrane Gynaecology and Fertility Group Register of trials, The Cochrane Central Register of Controlled Trials (CENTRAL; 2016 issue 4), MEDLINE, Embase, PsycINFO, DARE, the Web of Knowledge, OpenGrey, LILACS, PubMed and reference lists of articles. We also contacted experts and researchers in the field. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of oestrogenic preparations administered intravaginally in postmenopausal women for at least 12 weeks for the treatment of symptoms resulting from vaginal atrophy or vaginitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias and extracted the data. The primary review outcomes were improvement in symptoms (participant-assessed), and the adverse event endometrial thickness. Secondary outcomes were improvement in symptoms (clinician-assessed), other adverse events (breast disorders e.g. breast pain, enlargement or engorgement, total adverse events, excluding breast disorders) and adherence to treatment. We combined data to calculate pooled risk ratios (RRs) (dichotomous outcomes) and mean differences (MDs) (continuous outcomes) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I(2) statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. MAIN RESULTS: We included 30 RCTs (6235 women) comparing different intra-vaginal oestrogenic preparations with each other and with placebo. The evidence was low to moderate quality; limitations were poor reporting of study methods and serious imprecision (effect estimates with wide confidence intervals)1. Oestrogen ring versus other regimensOther regimens included oestrogen cream, oestrogen tablets and placebo. There was no evidence of a difference in improvement in symptoms (participant assessment) either between oestrogen ring and oestrogen cream (odds ratio (OR) 1.33, 95% CI 0.80 to 2.19, two RCTs, n = 341, I(2) = 0%, low-quality evidence) or between oestrogen ring and oestrogen tablets (OR 0.78, 95% CI 0.53 to 1.15, three RCTs, n = 567, I(2) = 0%, low-quality evidence). However, a higher proportion of women reported improvement in symptoms following treatment with oestrogen ring compared with placebo (OR 12.67, 95% CI 3.23 to 49.66, one RCT, n = 67). With respect to endometrial thickness, a higher proportion of women who received oestrogen cream showed evidence of increase in endometrial thickness compared to those who were treated with oestrogen ring (OR 0.36, 95% CI 0.14 to 0.94, two RCTs, n = 273; I(2) = 0%, low-quality evidence). This may have been due to the higher doses of cream used. 2. Oestrogen tablets versus other regimensOther regimens in this comparison included oestrogen cream, and placebo. There was no evidence of a difference in the proportions of women who reported improvement in symptoms between oestrogen tablets and oestrogen cream (OR 1.06, 95% CI 0.55 to 2.01, two RCTs, n = 208, I(2) = 0% low-quality evidence). A higher proportion of women who were treated with oestrogen tablets reported improvement in symptoms compared to those who received placebo using a fixed-effect model (OR 12.47, 95% CI 9.81 to 15.84, two RCTs, n = 1638, I(2) = 83%, low-quality evidence); however, using a random-effect model did not demonstrate any evidence of a difference in the proportions of women who reported improvement between the two treatment groups (OR 5.80, 95% CI 0.88 to 38.29). There was no evidence of a difference in the proportions of women with increase in endometrial thickness between oestrogen tablets and oestrogen cream (OR 0.31, 95% CI 0.06 to 1.60, two RCTs, n = 151, I(2) = 0%, low-quality evidence).3. Oestrogen cream versus other regimensOther regimens identified in this comparison included isoflavone gel and placebo. There was no evidence of a difference in the proportions of women with improvement in symptoms between oestrogen cream and isoflavone gel (OR 2.08, 95% CI 0.08 to 53.76, one RCT, n = 50, low-quality evidence). However, there was evidence of a difference in the proportions of women with improvement in symptoms between oestrogen cream and placebo with more women who received oestrogen cream reporting improvement in symptoms compared to those who were treated with placebo (OR 4.10, 95% CI 1.88 to 8.93, two RCTs, n = 198, I(2) = 50%, low-quality evidence). None of the included studies in this comparison reported data on endometrial thickness. AUTHORS' CONCLUSIONS: There was no evidence of a difference in efficacy between the various intravaginal oestrogenic preparations when compared with each other. However, there was low-quality evidence that intra-vaginal oestrogenic preparations improve the symptoms of vaginal atrophy in postmenopausal women when compared to placebo. There was low-quality evidence that oestrogen cream may be associated with an increase in endometrial thickness compared to oestrogen ring; this may have been due to the higher doses of cream used. However there was no evidence of a difference in the overall body of evidence in adverse events between the various oestrogenic preparations compared with each other or with placebo.

Intra-uterine insemination for unexplained subfertility.

BACKGROUND: Intra-uterine insemination (IUI) is a widely used fertility treatment for couples with unexplained subfertility. Although IUI is less invasive and less expensive thAppendixan in vitro fertilisation (IVF), the safety of IUI in combination with ovarian hyperstimulation (OH) is debated. The main concern about IUI treatment with OH is the increase in multiple pregnancy rate. This is an update of a Cochrane review (Veltman-Verhulst 2012) originally published in 2006 and updated in 2012. OBJECTIVES: To determine whether, for couples with unexplained subfertility, IUI improves the live birth rate compared with timed intercourse (TI), or expectant management, both with and without ovarian hyperstimulation (OH). SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (formerly Cochrane Menstrual Disorders and Subfertility Group) Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, inception to Issue 11, 2015), Ovid MEDLINE, Ovid EMBASE, PsycINFO and trial registers, all from inception to December 2015 and reference lists of articles. Authors of identified studies were contacted for missing or unpublished data. The evidence is current to December 2015. SELECTION CRITERIA: Truly randomised controlled trial (RCT) comparisons of IUI versus TI, in natural or stimulated cycles. Only couples with unexplained subfertility were included. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, quality assessment and data extraction. We extracted outcomes, and pooled data and, where possible, we carried out subgroup and sensitivity analyses. MAIN RESULTS: We included 14 trials including 1867 women. IUI versus TI or expectant management both in natural cycleLive birth rate (all cycles)There was no evidence of a difference in cumulative live births between the two groups (Odds Ratio (OR) 1.60, 95% confidence interval (CI) 0.92 to 2.78; 1 RCT; n = 334; moderate quality evidence). The evidence suggested that if the chance of a live birth in TI was assumed to be 16%, that of IUI would be between 15% and 34%.Multiple pregnancy rateThere was no evidence of a difference in multiple pregnancy rate between the two treatment groups (OR 0.50, 95% CI 0.04 to 5.53; 1 RCT; n = 334; moderate quality evidence). IUI versus TI or expectant management both in stimulated cycleLive birth rate (all cycles)There was no evidence of a difference between the two treatment groups (OR 1.59, 95% CI 0.88 to 2.88; 2 RCTs; n = 208; I(2) = 72%; moderate quality evidence). The evidence suggested that if the chance of achieving a live birth in TI was assumed to be 26%, the chance of a live birth with IUI would be between 23% and 50%.Multiple pregnancy rateThere was no evidence of a difference in multiple pregnancy rates between the two treatment groups (OR 1.46, 95% CI 0.55 to 3.87; 4 RCTs, n = 316; I(2) = 0%; low quality evidence). IUI in a natural cycle versus IUI in a stimulated cycle Live birth rate (all cycles)An increase in live birth rate was found for women who were treated with IUI in a stimulated cycle compared with those who underwent IUI in natural cycle (OR 0.48, 95% CI 0.29 to 0.82; 4 RCTs, n = 396; I(2) = 0%; moderate quality evidence). The evidence suggested that if the chance of a live birth in IUI in a stimulated cycle was assumed to be 25%, the chance of a live birth in IUI in a natural cycle would be between 9% and 21%.Multiple pregnancy rateThere was no evidence of a difference in multiple pregnancy rate between the two treatment groups (OR 0.33, 95% CI 0.01 to 8.70; 2 RCTs; n = 65; low quality evidence). IUI in a stimulated cycle versus TI or expectant management in a natural cycleLive birth rate (all cycles)There was no evidence of a difference in live birth rate between the two treatment groups (OR 0.82, 95% CI 0.45 to 1.49; 1 RCT; n = 253; moderate quality evidence). The evidence suggested that if the chance of a live birth in TI or expectant management in a natural cycle was assumed to be 24%, the chance of a live birth in IUI in a stimulated cycle would be between 12% and 32%.Multiple pregnancy rateThere was no evidence of a difference in multiple pregnancy rate between the two treatment groups (OR 2.00, 95% CI 0.18 to 22.34; 2 RCTs; n = 304; moderate quality evidence). IUI in natural cycle versus TI or expectant management in stimulated cycle Live birth rate (all cycles)There was evidence of an increase in live births for IUI (OR 1.95, 95% CI 1.10 to 3.44; 1 RCT, n = 342; moderate quality evidence). The evidence suggested that if the chance of a live birth in TI in a stimulated cycle was assumed to be 13%, the chance of a live birth in IUI in a natural cycle would be between 14% and 34%.Multiple pregnancy rateThere was no evidence of a difference in multiple pregnancy rate between the groups (OR 1.05, 95% CI 0.07 to 16.90; 1 RCT; n = 342; moderate quality evidence).The quality of the evidence was assessed using GRADE methods. Quality ranged from low to moderate, the main limitation being imprecision in the findings for both live birth and multiple pregnancy.. AUTHORS' CONCLUSIONS: This systematic review did not find conclusive evidence of a difference in live birth or multiple pregnancy in most of the comparisons for couples with unexplained subfertility treated with intra-uterine insemination (IUI) when compared with timed intercourse (TI), both with and without ovarian hyperstimulation (OH). There were insufficient studies to allow for pooling of data on the important outcome measures for each of the comparisons.

Gonadotrophin-releasing hormone antagonists for assisted reproductive technology.

BACKGROUND: Gonadotrophin-releasing hormone (GnRH) antagonists can be used to prevent a luteinizing hormone (LH) surge during controlled ovarian hyperstimulation (COH) without the hypo-oestrogenic side-effects, flare-up, or long down-regulation period associated with agonists. The antagonists directly and rapidly inhibit gonadotrophin release within several hours through competitive binding to pituitary GnRH receptors. This property allows their use at any time during the follicular phase. Several different regimens have been described including multiple-dose fixed (0.25 mg daily from day six to seven of stimulation), multiple-dose flexible (0.25 mg daily when leading follicle is 14 to 15 mm), and single-dose (single administration of 3 mg on day 7 to 8 of stimulation) protocols, with or without the addition of an oral contraceptive pill. Further, women receiving antagonists have been shown to have a lower incidence of ovarian hyperstimulation syndrome (OHSS). Assuming comparable clinical outcomes for the antagonist and agonist protocols, these benefits would justify a change from the standard long agonist protocol to antagonist regimens. This is an update of a Cochrane review first published in 2001, and previously updated in 2006 and 2011. OBJECTIVES: To evaluate the effectiveness and safety of gonadotrophin-releasing hormone (GnRH) antagonists compared with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception cycles. SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched from inception to May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, inception to 28 April 2015), Ovid MEDLINE (1966 to 28 April 2015), EMBASE (1980 to 28 April 2015), PsycINFO (1806 to 28 April 2015), CINAHL (to 28 April 2015) and trial registers to 28 April 2015, and handsearched bibliographies of relevant publications and reviews, and abstracts of major scientific meetings, for example the European Society of Human Reproduction and Embryology (ESHRE) and American Society for Reproductive Medicine (ASRM). We contacted the authors of eligible studies for missing or unpublished data. The evidence is current to 28 April 2015. SELECTION CRITERIA: Two review authors independently screened the relevant citations for randomised controlled trials (RCTs) comparing different GnRH agonist versus GnRH antagonist protocols in women undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias, and extracted the data. The primary review outcomes were live birth and ovarian hyperstimulation syndrome (OHSS). Other adverse effects (miscarriage and cycle cancellation) were secondary outcomes. We combined data to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I(2) statistic. We assessed the overall quality of the evidence for each comparison using GRADE methods. MAIN RESULTS: We included 73 RCTs, with 12,212 participants, comparing GnRH antagonist to long-course GnRH agonist protocols. The quality of the evidence was moderate: limitations were poor reporting of study methods.Live birthThere was no conclusive evidence of a difference in live birth rate between GnRH antagonist and long course GnRH agonist (OR 1.02, 95% CI 0.85 to 1.23; 12 RCTs, n = 2303, I(2)= 27%, moderate quality evidence). The evidence suggested that if the chance of live birth following GnRH agonist is assumed to be 29%, the chance following GnRH antagonist would be between 25% and 33%.OHSSGnRH antagonist was associated with lower incidence of any grade of OHSS than GnRH agonist (OR 0.61, 95% C 0.51 to 0.72; 36 RCTs, n = 7944, I(2) = 31%, moderate quality evidence). The evidence suggested that if the risk of OHSS following GnRH agonist is assumed to be 11%, the risk following GnRH antagonist would be between 6% and 9%.Other adverse effectsThere was no evidence of a difference in miscarriage rate per woman randomised between GnRH antagonist group and GnRH agonist group (OR 1.04, 95% CI 0.82 to 1.30; 33 RCTs, n = 7022, I(2) = 0%, moderate quality evidence).With respect to cycle cancellation, GnRH antagonist was associated with a lower incidence of cycle cancellation due to high risk of OHSS (OR 0.47, 95% CI 0.32 to 0.69; 19 RCTs, n = 4256, I(2) = 0%). However cycle cancellation due to poor ovarian response was higher in women who received GnRH antagonist than those who were treated with GnRH agonist (OR 1.32, 95% CI 1.06 to 1.65; 25 RCTs, n = 5230, I(2) = 68%; moderate quality evidence). AUTHORS' CONCLUSIONS: There is moderate quality evidence that the use of GnRH antagonist compared with long-course GnRH agonist protocols is associated with a substantial reduction in OHSS without reducing the likelihood of achieving live birth.

Nonsteroidal anti-inflammatory drugs for dysmenorrhoea.

BACKGROUND: Dysmenorrhoea is a common gynaecological problem consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea. Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs that act by blocking prostaglandin production. They inhibit the action of cyclooxygenase (COX), an enzyme responsible for the formation of prostaglandins. The COX enzyme exists in two forms, COX-1 and COX-2. Traditional NSAIDs are considered 'non-selective' because they inhibit both COX-1 and COX-2 enzymes. More selective NSAIDs that solely target COX-2 enzymes (COX-2-specific inhibitors) were launched in 1999 with the aim of reducing side effects commonly reported in association with NSAIDs, such as indigestion, headaches and drowsiness. OBJECTIVES: To determine the effectiveness and safety of NSAIDs in the treatment of primary dysmenorrhoea. SEARCH METHODS: We searched the following databases in January 2015: Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, November 2014 issue), MEDLINE, EMBASE and Web of Science. We also searched clinical trials registers (ClinicalTrials.gov and ICTRP). We checked the abstracts of major scientific meetings and the reference lists of relevant articles. SELECTION CRITERIA: All randomised controlled trial (RCT) comparisons of NSAIDs versus placebo, other NSAIDs or paracetamol, when used to treat primary dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, assessed their risk of bias and extracted data, calculating odds ratios (ORs) for dichotomous outcomes and mean differences for continuous outcomes, with 95% confidence intervals (CIs). We used inverse variance methods to combine data. We assessed the overall quality of the evidence using GRADE methods. MAIN RESULTS: We included 80 randomised controlled trials (5820 women). They compared 20 different NSAIDs (18 non-selective and two COX-2-specific) versus placebo, paracetamol or each other. NSAIDs versus placeboAmong women with primary dysmenorrhoea, NSAIDs were more effective for pain relief than placebo (OR 4.37, 95% CI 3.76 to 5.09; 35 RCTs, I(2) = 53%, low quality evidence). This suggests that if 18% of women taking placebo achieve moderate or excellent pain relief, between 45% and 53% taking NSAIDs will do so.However, NSAIDs were associated with more adverse effects (overall adverse effects: OR 1.29, 95% CI 1.11 to 1.51, 25 RCTs, I(2) = 0%, low quality evidence; gastrointestinal adverse effects: OR 1.58, 95% CI 1.12 to 2.23, 14 RCTs, I(2) = 30%; neurological adverse effects: OR 2.74, 95% CI 1.66 to 4.53, seven RCTs, I(2) = 0%, low quality evidence). The evidence suggests that if 10% of women taking placebo experience side effects, between 11% and 14% of women taking NSAIDs will do so. NSAIDs versus other NSAIDsWhen NSAIDs were compared with each other there was little evidence of the superiority of any individual NSAID for either pain relief or safety. However, the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials. Non-selective NSAIDs versus COX-2-specific selectorsOnly two of the included studies utilised COX-2-specific inhibitors (etoricoxib and celecoxib). There was no evidence that COX-2-specific inhibitors were more effective or tolerable for the treatment of dysmenorrhoea than traditional NSAIDs; however data were very scanty. NSAIDs versus paracetamolNSAIDs appeared to be more effective for pain relief than paracetamol (OR 1.89, 95% CI 1.05 to 3.43, three RCTs, I(2) = 0%, low quality evidence). There was no evidence of a difference with regard to adverse effects, though data were very scanty.Most of the studies were commercially funded (59%); a further 31% failed to state their source of funding. AUTHORS' CONCLUSIONS: NSAIDs appear to be a very effective treatment for dysmenorrhoea, though women using them need to be aware of the substantial risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea. We rated the quality of the evidence as low for most comparisons, mainly due to poor reporting of study methods.

Pelvic floor muscle training added to another active treatment versus the same active treatment alone for urinary incontinence in women.

BACKGROUND: Pelvic floor muscle training (PFMT) is a first-line conservative treatment for urinary incontinence in women. Other active treatments include: physical therapies (e.g. vaginal cones); behavioural therapies (e.g. bladder training); electrical or magnetic stimulation; mechanical devices (e.g. continence pessaries); drug therapies (e.g. anticholinergics (solifenacin, oxybutynin, etc.) and duloxetine); and surgical interventions including sling procedures and colposuspension. This systematic review evaluated the effects of adding PFMT to any other active treatment for urinary incontinence in women OBJECTIVES: To compare the effects of pelvic floor muscle training combined with another active treatment versus the same active treatment alone in the management of women with urinary incontinence. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 5 May 2015), and CINAHL (January 1982 to 6 May 2015), and the reference lists of relevant articles. SELECTION CRITERIA: We included randomised or quasi-randomised trials with two or more arms, of women with clinical or urodynamic evidence of stress urinary incontinence, urgency urinary incontinence or mixed urinary incontinence. One arm of the trial included PFMT added to another active treatment; the other arm included the same active treatment alone. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility and methodological quality and resolved any disagreement by discussion or consultation with a third party. We extracted and processed data in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Other potential sources of bias we incorporated into the 'Risk of bias' tables were ethical approval, conflict of interest and funding source. MAIN RESULTS: Thirteen trials met the inclusion criteria, comprising women with stress urinary incontinence (SUI), urgency urinary incontinence (UUI) or mixed urinary incontinence (MUI); they compared PFMT added to another active treatment (585 women) with the same active treatment alone (579 women). The pre-specified comparisons were reported by single trials, except bladder training, which was reported by two trials, and electrical stimulation, which was reported by three trials. However, only two of the three trials reporting electrical stimulation could be pooled, as one of the trials did not report any relevant data. We considered the included trials to be at unclear risk of bias for most of the domains, predominantly due to the lack of adequate information in a number of trials. This affected our rating of the quality of evidence. The majority of the trials did not report the primary outcomes specified in the review (cure or improvement, quality of life) or measured the outcomes in different ways. Effect estimates from small, single trials across a number of comparisons were indeterminate for key outcomes relating to symptoms, and we rated the quality of evidence, using the GRADE approach, as either low or very low. More women reported cure or improvement of incontinence in two trials comparing PFMT added to electrical stimulation to electrical stimulation alone, in women with SUI, but this was not statistically significant (9/26 (35%) versus 5/30 (17%); risk ratio (RR) 2.06, 95% confidence interval (CI) 0.79 to 5.38). We judged the quality of the evidence to be very low. There was moderate-quality evidence from a single trial investigating women with SUI, UUI or MUI that a higher proportion of women who received a combination of PFMT and heat and steam generating sheet reported a cure compared to those who received the sheet alone: 19/37 (51%) versus 8/37 (22%) with a RR of 2.38, 95% CI 1.19 to 4.73). More women reported cure or improvement of incontinence in another trial comparing PFMT added to vaginal cones to vaginal cones alone, but this was not statistically significant (14/15 (93%) versus 14/19 (75%); RR 1.27, 95% CI 0.94 to 1.71). We judged the quality of the evidence to be very low. Only one trial evaluating PFMT when added to drug therapy provided information about adverse events (RR 0.84, 95% CI 0.45 to 1.60; very low-quality evidence).With regard to condition-specific quality of life, there were no statistically significant differences between women (with SUI, UUI or MUI) who received PFMT added to bladder training and those who received bladder training alone at three months after treatment, on either the Incontinence Impact Questionnaire-Revised scale (mean difference (MD) -5.90, 95% CI -35.53 to 23.73) or on the Urogenital Distress Inventory scale (MD -18.90, 95% CI -37.92 to 0.12). A similar pattern of results was observed between women with SUI who received PFMT plus either a continence pessary or duloxetine and those who received the continence pessary or duloxetine alone. In all these comparisons, the quality of the evidence for the reported critical outcomes ranged from moderate to very low. AUTHORS' CONCLUSIONS: This systematic review found insufficient evidence to state whether or not there were additional effects by adding PFMT to other active treatments when compared with the same active treatment alone for urinary incontinence (SUI, UUI or MUI) in women. These results should be interpreted with caution as most of the comparisons were investigated in small, single trials. None of the trials in this review were large enough to provide reliable evidence. Also, none of the included trials reported data on adverse events associated with the PFMT regimen, thereby making it very difficult to evaluate the safety of PFMT.

Pelvic floor muscle training added to another active treatment versus the same active treatment alone for urinary incontinence in women.

BACKGROUND: Pelvic floor muscle training (PFMT) is a first-line conservative treatment for urinary incontinence in women. Other active treatments include: physical therapies (e.g. vaginal cones); behavioural therapies (e.g. bladder training); electrical or magnetic stimulation; mechanical devices (e.g. continence pessaries); drug therapies (e.g. anticholinergics (solifenacin, oxybutynin, etc.) and duloxetine); and surgical interventions including sling procedures and colposuspension. This systematic review evaluated the effects of adding PFMT to any other active treatment for urinary incontinence in women OBJECTIVES: To compare the effects of pelvic floor muscle training combined with another active treatment versus the same active treatment alone in the management of women with urinary incontinence. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, and handsearching of journals and conference proceedings (searched 28 February 2013), EMBASE (January 1947 to 2013 Week 9), CINAHL (January 1982 to 5 March 2013), ClinicalTrials.gov (searched 30 May 2013), WHO ICTRP (searched 3 June 2013) and the reference lists of relevant articles. SELECTION CRITERIA: We included randomised or quasi-randomised trials with two or more arms in women with clinical or urodynamic evidence of stress urinary incontinence, urgency urinary incontinence or mixed urinary incontinence. One arm of the trial included PFMT added to another active treatment; the other arm included the same active treatment alone. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility and methodological quality and resolved any disagreement by discussion or consultation with a third party. We extracted and processed data in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Other potential sources of bias we incorporated into the 'Risk of bias' tables were ethical approval, conflict of interest and funding source. MAIN RESULTS: Eleven trials met the eligibility criteria for inclusion, comprising women with stress urinary incontinence (SUI), urgency urinary incontinence (UUI) or mixed urinary incontinence (MUI), and they compared PFMT added to another active treatment (494 women) with the same active treatment alone (490 women). The pre-specified comparisons were reported by single trials except electrical stimulation which was reported by two trials. However, the two trials reporting electrical stimulation could not be pooled as one of the trials did not report any relevant data. We considered the included trials to be at unclear risk of bias for most of the domains, predominantly due to the lack of adequate information in a number of trials. This affected our rating of the quality of evidence. The majority of the trials did not report the primary outcomes specified in the review (cure/improvement, quality of life) or measured the outcomes in different ways. Effect estimates from small, single trials across a number of comparisons were indeterminate for key outcomes relating to symptoms and we rated the quality of evidence, using the GRADE approach, as either low or very low. There was moderate-quality evidence from a single trial investigating women with SUI, UUI or MUI that a higher proportion of women who received a combination of PFMT and heat and steam generating sheet reported cure compared to those who received the sheet alone: 19/37 (51%) versus 8/37 (22%) with a risk ratio (RR) of 2.38, 95% confidence interval (CI) 1.19 to 4.73). More women reported cure or improvement of incontinence in another trial comparing PFMT added to vaginal cones to vaginal cones alone: 14/15 (93%) versus 14/19 (75%), but this was not statistically significant (RR 1.27, 95% CI 0.94 to 1.71). We judged the quality of the evidence to be very low. Only one trial evaluating PFMT when added to drug therapy provided information about adverse events (RR 0.84, 95% CI 0.45 to 1.60; very low-quality evidence).With regard to condition-specific quality of life, there were no statistically significant differences between women (with SUI, UUI or MUI) who received PFMT added to bladder training and those who received bladder training alone at three months after treatment either on the Incontinence Impact Questionnaire-Revised scale (mean difference (MD) -5.90, 95% CI -35.53 to 23.73) or on the Urogenital Distress Inventory scale (MD -18.90, 95% CI -37.92 to 0.12). A similar pattern of results was observed between women with SUI who received PFMT plus either a continence pessary or duloxetine and those who received the continence pessary or duloxetine alone. In all these comparisons, the quality of the evidence for the reported critical outcomes ranged from moderate to very low. AUTHORS' CONCLUSIONS: This systematic review found insufficient evidence to state whether or not there were additional effects of adding PFMT to other active treatment when compared with the same active treatment alone for urinary incontinence (SUI, UUI or MUI) in women. These results should be interpreted with caution as most of the comparisons were investigated in small, single trials. None of the trials in this review were large enough to provide reliable evidence. Also, none of the included trials reported data on adverse events associated with the PFMT regimen, thereby making it very difficult to evaluate the safety of PFMT.

New Zealand's Integration-Based Policy for Driving Local Health System Improvement - Which Conditions Underpin More Successful Implementation?

INTRODUCTION: The System Level Framework (SLMF) is a policy introduced by New Zealand's Ministry of Health in 2016 with the aim of improving health outcomes by stimulating inter-organisational integration at the local level. We sought to understand which conditions that vary at the local level are most important in shaping successful implementation of this novel and internationally significant policy initiative relevant to integrated care. STRATEGY AND METHODS: We conducted 50 interviews with managers and clinicians who were directly involved in SLM implementation during 2018. Interview data was supplemented with the SLM Improvement Plans of all districts over the first three years of implementation. We used Qualitative Comparative Analysis (QCA) to identify the combinations and configurations of necessary and sufficient conditions of successful implementation. RESULTS: We found that the strength of formal and informal organisational relationships at the local level were critical conditions for implementation success, and that while fidelity to the policy programme was necessary, it was not sufficient. Broader contextual features such as population size and complexity of the organisational environment were less important. The SLMF was able to deepen and widen inter-organisational collaboration where it already existed but could not mitigate the legacies of weaker relationships. DISCUSSION: The two dimensions of implementation success, 'Maturity of SLM Improvement Plan Processes' and 'Data Sophistication and Use' were closely related. Broadly, our findings support the contention that integrated approaches to health system improvement at the local level require collaborative, trust-based approaches with an emphasis on iterative learning, including the willingness to share data between organisations. CONCLUSION: In the context of integrated care, our findings support the need to focus on establishing the conditions that build collaborative governance in addition to strengthening it when it already exists.

Impact of training and professional development on health management and leadership competence.

PURPOSE: Training to improve health management and leadership competence is recommended. However, there is limited evidence showing the impact of training on competence. The purpose of this paper is to evaluate the evidence for the impact of training and professional development on health management and leadership competence. DESIGN/METHODOLOGY/APPROACH: A systematic review was conducted using a mixed-methods design. Studies using qualitative, quantitative or mixed-methods design were included. The following electronic databases were searched to October 2018: CENTRAL, CINAHL, EMBASE, ERIC, NEDLINE and PsycINFO. Study eligibility and methodological quality were assessed independently by two review authors. Data from qualitative studies were synthesised using thematic analysis. For quantitative studies, odds ratio (OR) or mean difference (MD) and 95% confidence interval (CI) were calculated for each intervention. Where appropriate, qualitative and quantitative data were integrated into a single synthesis using Bayesian methods. FINDINGS: In total, 19 studies were identified for inclusion in the review. Training and professional development interventions using flexible, multiple training techniques tailored to organisational contexts can improve individual competence and performance. Such training is typified by a leadership development programme. There was insufficient evidence to determine the effects of interventions on organisational performance. ORIGINALITY/VALUE: This is the first systematic review evaluating the impact of training and professional development interventions on health management and leadership competence.

Outcomes and Impact of Training and Development in Health Management and Leadership in Relation to Competence in Role: A Mixed-Methods Systematic Review Protocol.

BACKGROUND: The need for competence training and development in health management and leadership workforces has been emphasised. However, evidence of the outcomes and impact of such training and development has not been systematically assessed. The aim of this review is to synthesise the available evidence of the outcomes and impact of training and development in relation to the competence of health management and leadership workforces. This is with a view to enhancing the development of evidence-informed programmes to improve competence. METHODS AND ANALYSIS: A systematic review will be undertaken using a mixed-methods research synthesis to identify, assess and synthesise relevant empirical studies. We will search relevant electronic databases and other sources for eligible studies. The eligibility of studies for inclusion will be assessed independently by two review authors. Similarly, the methodological quality of the included studies will be assessed independently by two review authors using appropriate validated instruments. Data from qualitative studies will be synthesised using thematic analysis. For quantitative studies, appropriate effect size estimate will be calculated for each of the interventions. Where studies are sufficiently similar, their findings will be combined in meta-analyses or meta-syntheses. Findings from quantitative syntheses will be converted into textual descriptions (qualitative themes) using Bayesian method. Textual descriptions and results of the initial qualitative syntheses that are mutually compatible will be combined in mixed-methods syntheses. DISCUSSION: The outcome of data collection and analysis will lead, first, to a descriptive account of training and development programmes used to improve the competence of health management and leadership workforces and the acceptability of such programmes to participants. Secondly, the outcomes and impact of such programmes in relation to participants' competence as well as individual and organisational performance will be identified. If possible, the relationship between health contexts and the interventions required to improve management and leadership competence will be examined.