Guideline No. 431: Postpartum Hemorrhage and Hemorrhagic Shock.

OBJECTIVE: This guideline aims to provide evidence for prevention, recognition, and treatment of postpartum hemorrhage including severe hemorrhage leading to hemorrhagic shock. TARGET POPULATION: All pregnant patients. BENEFITS, HARMS, AND COSTS: Appropriate recognition and treatment of postpartum hemorrhage can prevent serious morbidity while reducing costs to the health care system by minimizing more costly interventions and length of hospital stays. EVIDENCE: Medical literature, PubMed, ClinicalTrials.gov, the Cochrane Database, and grey literature were searched for articles, published between 2012 and 2021, on postpartum hemorrhage, uterotonics, obstetrical hemorrhage, and massive hemorrhage protocols. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: All members of the health care team who care for labouring or postpartum women, including, but not restricted to, nurses, midwives, family physicians, obstetricians, and anesthesiologists.

Standardizing definitions and reporting guidelines for the infertility core outcome set: an international consensus development study† ‡.

STUDY QUESTION: Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? SUMMARY ANSWER: Consensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed. WHAT IS KNOWN ALREADY: Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. STUDY DESIGN, SIZE, DURATION: Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. MAIN RESULTS AND THE ROLE OF CHANCE: Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries. WIDER IMPLICATIONS OF THE FINDINGS: A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. E.H.Y.N. reports research sponsorship from Merck. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials Initiative: 1023.

Menorrhagia.

INTRODUCTION: Menorrhagia (also known as heavy menstrual bleeding) limits normal activities, affects quality of life, and causes anaemia in two-thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may be associated with idiopathic menorrhagia and with heavy bleeding due to fibroids, adenomyosis, or use of intrauterine devices (IUDs). Fibroids have been found in 10% of women with menorrhagia overall and in 40% of women with severe menorrhagia; but half of women having a hysterectomy for menorrhagia are found to have a normal uterus. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of surgical treatments for menorrhagia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). RESULTS: At this update, searching of electronic databases retrieved 205 studies. After deduplication and removal of conference abstracts, 102 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 56 studies and the further review of 46 full publications. Of the 46 full articles evaluated, three systematic reviews and five RCTs were added at this update. We performed a GRADE evaluation for 30 PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for three surgical interventions based on information about the effectiveness and safety of dilatation and curettage, endometrial destruction (resection or ablation), and hysterectomy.

Nitric oxide donors for treating preterm labour.

BACKGROUND: A number of tocolytics have been advocated for the treatment of threatened preterm labour in order to delay birth. The rationale is that a delay in birth may be associated with improved neonatal morbidity or mortality. Nitric oxide donors, such as nitroglycerin, have been used to relax the uterus. This review addresses their efficacy, adverse effects and influence on neonatal outcome. OBJECTIVES: To determine whether nitric oxide donors administered in threatened preterm labour are associated with a delay in birth, adverse effects or improved neonatal outcome. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 December 2013). SELECTION CRITERIA: Randomised controlled trials of nitric oxide donors administered for tocolysis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Twelve trials, including a total of 1227 women at risk of preterm labour, contributed data to this updated review. The methodological quality of trials was mixed; trials comparing nitric oxide donors with other types of tocolytics were not blinded and this may have had an impact on findings.Three studies compared nitric oxide donors (glyceryl trinitrate (GTN)) with placebo. There was no significant evidence that nitric oxide donors prolonged pregnancy beyond 48 hours (average risk ratio (RR) 1.19, 95% confidence interval (CI) 0.74 to 1.90, two studies, 186 women), and although for most adverse effects there was no significant difference between groups, women in the active treatment group in one study were at higher risk of experiencing a headache. For infant outcomes there was no significant evidence that nitric oxide donors reduced the risk of neonatal death or serious morbidity (stillbirth RR 0.36, 95% CI 0.01 to 8.59, one study, 153 infants; neonatal death RR 0.43, 95% CI 0.06 to 2.89, two studies, 186 infants). One study, using a composite outcome, reported a reduced risk of serious adverse outcomes for infants in the GTN group which approached statistical significance (RR 0.29, 95% CI 0.08 to 1.00, 153 infants). Overall, these studies were underpowered to identify differences between groups for most outcomes.When nitric oxide donors were compared with other tocolytic drugs there was no significant evidence that nitric oxide donors performed better than other tocolytics (betamimetics, magnesium sulphate, a calcium channel blocker or a combination of tocolytics) in terms of pregnancy prolongation, although nitric oxide donors appeared to be associated with a reduction in most adverse effects, apart from headache. There was no significant difference between groups for infant morbidity or mortality outcomes. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to support the routine administration of nitric oxide donors in the treatment of threatened preterm labour.

Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels, which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea. OBJECTIVES: The primary objective of this review was to investigate the effectiveness of NSAIDs in achieving a reduction in menstrual blood loss in women of reproductive years with HMB. SEARCH METHODS: We searched the Cochrane Menstrual Disorders & Subfertility Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL in July 2012 and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of individual NSAIDs or combined with other medical therapy with either each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment-induced) causes for their heavy menstrual blood loss. DATA COLLECTION AND ANALYSIS: Eighteen RCTs were identified that fulfilled the inclusion criteria for this review and data were extracted independently. Odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data of nine trials. The results of the remaining seven cross-over trials with data unsuitable for pooling, one trial with skewed data and one trial with missing variances were described in data tables. MAIN RESULTS: As a group, NSAIDs were more effective than placebo at reducing HMB but less effective than either tranexamic acid, danazol or the levonorgestrel-releasing intrauterine system (LNG IUS). Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs but this did not appear to affect the acceptability of treatment. There were no statistically significant differences between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone-releasing intrauterine system (Progestasert), oral contraceptive pill (OCC)) but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. AUTHORS' CONCLUSIONS: NSAIDs reduce HMB when compared with placebo but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCC or another type of intrauterine system, Progestasert.

Menorrhagia.

INTRODUCTION: Menorrhagia limits normal activities, and causes anaemia in two-thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may be associated with idiopathic menorrhagia, and with heavy bleeding due to fibroids, adenomyosis, or use of intrauterine devices (IUDs). Fibroids have been found in 10% of women with menorrhagia overall, and in 40% of women with severe menorrhagia; but half of women having a hysterectomy for menorrhagia are found to have a normal uterus. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments for menorrhagia? What are the effects of surgical treatments for menorrhagia? What are the effects of endometrial thinning before endometrial destruction in treating menorrhagia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations, such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 39 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following medical interventions: combined pill, danazol, etamsylate, gonadorelin analogues, intrauterine progesterone, non-steroidal anti-inflammatory drugs (NSAIDs), progestogens, and the following surgical interventions: dilatation and curettage, endometrial destruction, and hysterectomy.

Recurrent miscarriage.

INTRODUCTION: Recurrent miscarriage is the spontaneous loss of three or more consecutive pregnancies with the same biological father in the first trimester, and affects 1% to 2% of women, half of whom have no identifiable cause. Overall, 75% of affected women will have a successful subsequent pregnancy, but this rate falls for older mothers and with increasing number of miscarriages. Antiphospholipid syndrome, with anticardiolipin or lupus anticoagulant antibodies, is present in 15% of women with recurrent first and second trimester miscarriage. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for unexplained recurrent miscarriage? What are the effects of treatments for recurrent miscarriage caused by antiphospholipid syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: aspirin (low dose), bed-rest, corticosteroids, early scanning in subsequent pregnancies, heparin plus low-dose aspirin, human chorionic gonadotrophin, intravenous immunoglobulin treatment, lifestyle adaptation, oestrogen, paternal white cell immunisation, progesterone, trophoblastic membrane infusion, and vitamin supplementation.

Managing perimenopausal menorrhagia.

Menorrhagia is a significant health problem for many women. It increases with age and peaks during the perimenopause. Although historically, hysterectomy as been the mainstay for treatment there are many effective medical and surgical alternatives to hysterectomy that may be eminently suitable for perimenopausal women as menopause will intervene in due course. The incidence, aetiology, initial management and effective treatment options are discussed in this review article.

Menorrhagia.

INTRODUCTION: Menorrhagia limits normal activities, and causes anaemia in two thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may be associated with idiopathic menorrhagia, and with heavy bleeding due to fibroids, adenomyosis, or use of intrauterine devices (IUDs). Fibroids have been found in 10% of women with menorrhagia overall, and in 40% of women with severe menorrhagia; but half of women having a hysterectomy for menorrhagia are found to have a normal uterus. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments for menorrhagia? What are the effects of surgical treatments for menorrhagia? What are the effects of endometrial thinning before endometrial destruction in treating menorrhagia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 39 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following medical interventions: combined pill, danazol, etamsylate, gonadorelin analogues, intrauterine progesterone, non-steroidal inflammatory drugs (NSAIDs), progestogens, and the following surgical interventions: dilatation and curretage, endometrial destruction, and hysterectomy.

Recurrent miscarriage.

INTRODUCTION: Recurrent miscarriage is the spontaneous loss of three or more consecutive pregnancies with the same biological father in the first trimester, and affects 1-2% of women, half of whom have no identifiable cause. Overall, 75% of affected women will have a successful subsequent pregnancy, but this rate falls for older mothers and with increasing number of miscarriages. Antiphospholipid syndrome, with anticardiolipin or lupus anticoagulant antibodies, is present in 15% of women with recurrent first and second trimester miscarriage. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for unexplained recurrent miscarriage? What are the effects of treatments for recurrent miscarriage caused by antiphospholipid syndrome? We searched: Medline, Embase, The Cochrane Library and other important databases up to April 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: aspirin (low dose), bed rest, corticosteroids, early scanning in subsequent pregnancies, heparin plus low-dose aspirin, human chorionic gonadotrophin, intravenous immunoglobulin treatment, lifestyle adaptation, oestrogen, paternal white cell immunisation, progesterone, trophoblastic membrane infusion, and vitamin supplementation.

Medical management of perimenopausal menorrhagia: an evidence-based approach.

About one-third of women report heavy menstrual bleeding at some time in their lives. Menstrual blood loss increases with age. Menorrhagia is usually defined as heavy but regular menstrual bleeding of over 80 ml/cycle. Complaints of menorrhagia are common. Several medical therapies are suitable for perimenopausal women with either regular or irregular heavy bleeding. The most effective is intrauterine levonorgestrel. Other options are oral progestogens, the combined oral contraceptive pill, tranexamic acid, mefenamic acid, danazol and gonadotrophin-releasing hormone (GnRH) analogues. Systematic reviews and randomized controlled trials are discussed.