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Fertility and Sterility Oct 2021To quantify the efficacy of medical management of uterine arteriovenous malformation (AVM) and compare efficacy between different classes of medication. In addition, we... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To quantify the efficacy of medical management of uterine arteriovenous malformation (AVM) and compare efficacy between different classes of medication. In addition, we evaluated for factors associated with treatment success and pregnancy outcomes after medical management.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Thirty-two studies representing 121 premenopausal women with medically-treated uterine AVM were identified via database searches of MEDLINE, Embase, Web of Science, and cited references.
INTERVENTION(S)
Medical treatment with progestins, gonadotropin-releasing hormone agonists (GnRH-a), methotrexate, combined hormonal contraception , uterotonics, danazol, or combination of the above.
MAIN OUTCOME MEASURE(S)
Primary outcome of treatment success was defined as AVM resolution without subsequent procedural interventions. Secondary outcome was treatment complication (readmission or transfusion).
RESULT(S)
The overall success rate of medical management was 88% (106/121). After adjusting for clustering effects, success rates for progestin (82.5%; 95% confidence interval [CI], 70.1%-90.4%), GnRH-a (89.3%; 99% CI, 71.4%-96.5%) and methotrexate (90.0%; 99% CI, 55.8%-98.8%) were significantly different from the null hypothesis of 50% success. The agents with the lowest adjusted proportion of complications were progestins (10.0%; 99% CI, 3.3%-26.8%) and GnRH-a (10.7%; 99% CI, 3.5%-28.4%). No clinical factors were found to predict treatment success. Twenty-six subsequent pregnancies are described, with no reported recurrences of AVM.
CONCLUSION(S)
Medical management for uterine AVM is a reasonable approach in a well selected patient. These data should be interpreted in the context of significant publication bias.
Topics: Arteriovenous Fistula; Blood Transfusion; Clinical Decision-Making; Female; Humans; Patient Readmission; Patient Selection; Pregnancy; Pregnancy Rate; Risk Assessment; Risk Factors; Treatment Outcome; Uterine Artery; Uterus
PubMed: 34130801
DOI: 10.1016/j.fertnstert.2021.05.095 -
Research and Practice in Thrombosis and... May 2021Randomized controlled trials on menopausal hormone therapy in humans have not confirmed the benefit of estrogens on cardiovascular disease found in animal studies....
BACKGROUND
Randomized controlled trials on menopausal hormone therapy in humans have not confirmed the benefit of estrogens on cardiovascular disease found in animal studies. Flawed methodology or publication bias in animal studies may explain the dicrepancy.
OBJECTIVES
The aim of this study was to investigate whether publication of the randomized controlled trials Heart and Estrogen/Progestin Replacement Study and Women's Health Initiative influenced study authors' assessment of research findings (confirmation bias) as well as to investigate publication bias and small-study effects in animal studies of estrogen effects on atherosclerosis.
METHODS
The data source for this study was PubMed from inception to 2018. We selected animal studies with cardiovascular outcomes comparing 17-β-estradiol, its natural metabolites, or conjugated equine estrogen with control. Qualitative data were extracted on authors' conclusions about estrogen effects on cardiovascular disease, as well as quantitative data for atherosclerosis outcomes. Fixed- and random-effects meta-analyses were used. Publication bias/small-study effects were assessed using funnel plots and Egger's regression. Trim-and-fill plots and extrapolation from Egger's regression were used to adjust for publication bias. The main outcomes and measures were the primary study authors' interpretation of their own results, and estrogen effects on cardiovascular disease in general before and after publication of the Women's health Initiative study (2003). The effects of estrogens on atherosclerosis were measured as standardized mean difference between intervention and control.
RESULTS
Of 1925 studies retrieved, 360 were eligible for analyses. Study-specific statements concluded that estrogens were protective against cardiovascular disease in 75% of studies before 2003 and 78% after, but the percentage of general statements about estrogens being cardioprotective changed from 70% to 40%. Meta-analyses showed less atherosclerosis in estrogen-treated animals. Extremely skewed funnel plots and < .01 in Egger's regression suggested publication bias and/or exaggerated effects in small studies, which was more pronounced after 2002. There was substantial heterogeneity of effects ( = 68%-86%) overall and in all subgroups except cynomolgus monkeys ( = 9%), the only animal subgroup without clear bias. Adjusting for publication bias, overall estimates of estrogen effects on atherosclerosis were close to null effect.
CONCLUSIONS
We found substantial evidence of publication bias but not of confirmation bias. Publication bias and flawed small studies may partly explain why findings differ between animal studies and clinical trials on the effect of estrogens on cardiovascular disease.
PubMed: 34013151
DOI: 10.1002/rth2.12507 -
The Cochrane Database of Systematic... Apr 2021Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime, and 15% to 20% of pregnancies ending in a miscarriage. Progesterone has an important role in maintaining a pregnancy, and supplementation with different progestogens in early pregnancy has been attempted to rescue a pregnancy in women with early pregnancy bleeding (threatened miscarriage), and to prevent miscarriages in asymptomatic women who have a history of three or more previous miscarriages (recurrent miscarriage).
OBJECTIVES
To estimate the relative effectiveness and safety profiles for the different progestogen treatments for threatened and recurrent miscarriage, and provide rankings of the available treatments according to their effectiveness, safety, and side-effect profile.
SEARCH METHODS
We searched the following databases up to 15 December 2020: Cochrane Central Register of Controlled Trials, Ovid MEDLINE(R), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies.
SELECTION CRITERIA
We included all randomised controlled trials assessing the effectiveness or safety of progestogen treatment for the prevention of miscarriage. Cluster-randomised trials were eligible for inclusion. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. We excluded quasi- and non-randomised trials.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed the trials for inclusion and risk of bias, extracted data and checked them for accuracy. We performed pairwise meta-analyses and indirect comparisons, where possible, to determine the relative effects of all available treatments, but due to the limited number of included studies only direct or indirect comparisons were possible. We estimated the relative effects for the primary outcome of live birth and the secondary outcomes including miscarriage (< 24 weeks of gestation), preterm birth (< 37 weeks of gestation), stillbirth, ectopic pregnancy, congenital abnormalities, and adverse drug events. Relative effects for all outcomes are reported separately by the type of miscarriage (threatened and recurrent miscarriage). We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Our meta-analysis included seven randomised trials involving 5,682 women, and all provided data for meta-analysis. All trials were conducted in hospital settings. Across seven trials (14 treatment arms), the following treatments were used: three arms (21%) used vaginal micronized progesterone; three arms (21%) used dydrogesterone; one arm (7%) used oral micronized progesterone; one arm (7%) used 17-α-hydroxyprogesterone, and six arms (43%) used placebo. Women with threatened miscarriage Based on the relative effects from the pairwise meta-analysis, vaginal micronized progesterone (two trials, 4090 women, risk ratio (RR) 1.03, 95% confidence interval (CI) 1.00 to 1.07, high-certainty evidence), and dydrogesterone (one trial, 406 women, RR 0.98, 95% CI 0.89 to 1.07, moderate-certainty evidence) probably make little or no difference to the live birth rate when compared with placebo for women with threatened miscarriage. No data are available to assess the effectiveness of 17-α-hydroxyprogesterone or oral micronized progesterone for the outcome of live birth in women with threatened miscarriage. The pre-specified subgroup analysis by number of previous miscarriages is only possible for vaginal micronized progesterone in women with threatened miscarriage. In women with no previous miscarriages and early pregnancy bleeding, there is probably little or no improvement in the live birth rate (RR 0.99, 95% CI 0.95 to 1.04, high-certainty evidence) when treated with vaginal micronized progesterone compared to placebo. However, for women with one or more previous miscarriages and early pregnancy bleeding, vaginal micronized progesterone increases the live birth rate compared to placebo (RR 1.08, 95% CI 1.02 to 1.15, high-certainty evidence). Women with recurrent miscarriage Based on the results from one trial (826 women) vaginal micronized progesterone (RR 1.04, 95% CI 0.95 to 1.15, high-certainty evidence) probably makes little or no difference to the live birth rate when compared with placebo for women with recurrent miscarriage. The evidence for dydrogesterone compared with placebo for women with recurrent miscarriage is of very low-certainty evidence, therefore the effects remain unclear. No data are available to assess the effectiveness of 17-α-hydroxyprogesterone or oral micronized progesterone for the outcome of live birth in women with recurrent miscarriage. Additional outcomes All progestogen treatments have a wide range of effects on the other pre-specified outcomes (miscarriage (< 24 weeks of gestation), preterm birth (< 37 weeks of gestation), stillbirth, ectopic pregnancy) in comparison to placebo for both threatened and recurrent miscarriage. Moderate- and low-certainty evidence with a wide range of effects suggests that there is probably no difference in congenital abnormalities and adverse drug events with vaginal micronized progesterone for threatened (congenital abnormalities RR 1.00, 95% CI 0.68 to 1.46, moderate-certainty evidence; adverse drug events RR 1.07 95% CI 0.81 to 1.39, moderate-certainty evidence) or recurrent miscarriage (congenital abnormalities 0.75, 95% CI 0.31 to 1.85, low-certainty evidence; adverse drug events RR 1.46, 95% CI 0.93 to 2.29, moderate-certainty evidence) compared with placebo. There are limited data and very low-certainty evidence on congenital abnormalities and adverse drug events for the other progestogens.
AUTHORS' CONCLUSIONS
The overall available evidence suggests that progestogens probably make little or no difference to live birth rate for women with threatened or recurrent miscarriage. However, vaginal micronized progesterone may increase the live birth rate for women with a history of one or more previous miscarriages and early pregnancy bleeding, with likely no difference in adverse events. There is still uncertainty over the effectiveness and safety of alternative progestogen treatments for threatened and recurrent miscarriage.
Topics: Abortion, Habitual; Abortion, Spontaneous; Bias; Birth Rate; Dydrogesterone; Female; Humans; Hydroxyprogesterones; Live Birth; Network Meta-Analysis; Placebos; Pregnancy; Progesterone; Progestins; Randomized Controlled Trials as Topic; Stillbirth
PubMed: 33872382
DOI: 10.1002/14651858.CD013792.pub2 -
BMC Pregnancy and Childbirth Mar 2021Retained placenta represents a cause of maternal morbidity and mortality affecting 0.5-3% of all vaginal deliveries. The unpredictability of this condition makes...
BACKGROUND
Retained placenta represents a cause of maternal morbidity and mortality affecting 0.5-3% of all vaginal deliveries. The unpredictability of this condition makes difficult to develop predictive and preventive strategies to apply in clinical practice. This analysis collected and analyzed all known risk factors related to this obstetric complication.
METHODS
A systematic literature review for all original research articles published between 1990 and 2020 was performed. Observational studies about retained placenta risk factors published in English language were considered eligible. Conference abstracts, untraceable articles and studies focused on morbidly adherent placenta were excluded. The included articles were screened to identify study design, number of enrolled patients and retained placenta risk factors investigated. All stages of the revision followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement.
RESULTS
Thirty-five studies met the inclusion criteria. The reported retained placenta prevalence ranged from 0.5 to 4.8%. Maternal age, previous cesarean sections, previous dilation and curettage, previous retained placenta, labor induction, resulted as the most recurrent, independent risk factors for retained placenta. Previous estro-progestins therapy, morphological placental features (weight, shape, insertion of umbilical cord, implantation site), endometriosis, Assisted Reproductive Technologies, Apgar score are fascinating new proposal risk factors.
CONCLUSIONS
Old and new data are not enough robust to draw firm conclusions. Prospective and well-designed studies, based on a well agreed internationally retained placenta definition, are needed in order to clarify this potential dramatic and life-threatening condition.
Topics: Delivery, Obstetric; Female; Humans; Placenta, Retained; Pregnancy; Prevalence; Prospective Studies; Risk Assessment; Risk Factors
PubMed: 33789611
DOI: 10.1186/s12884-021-03721-9 -
Lancet (London, England) Mar 2021Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.
METHODS
We did a systematic review of randomised trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299.
FINDINGS
Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk [RR] 0·78, 95% CI 0·68-0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68-1·01), and oral progesterone (two trials, 181 women; 0·60, 0·40-0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84-1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92-1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture <34 weeks RR 1·59, 95% CI 1·15-2·22), but we found no consistent evidence of benefit or harm for other outcomes with either vaginal progesterone or 17-OHPC.
INTERPRETATION
Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence.
FUNDING
Patient-Centered Outcomes Research Institute.
Topics: 17-alpha-Hydroxyprogesterone; Administration, Intravaginal; Decision Making, Shared; Female; Humans; Infant, Newborn; Injections, Intramuscular; Pregnancy; Pregnancy Outcome; Pregnancy, High-Risk; Premature Birth; Progesterone; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 33773630
DOI: 10.1016/S0140-6736(21)00217-8 -
Molecules (Basel, Switzerland) Jan 2021Phytochemical contents of honey are presumed to be beneficial to the female reproductive system (FRS). However, the biological effects of honey supplementation (HS) in...
Phytochemical contents of honey are presumed to be beneficial to the female reproductive system (FRS). However, the biological effects of honey supplementation (HS) in vivo on the FRS remain unclear. This review aims to investigate the current literature on the effects of HS on the FRS, particularly on the sex hormone profile and reproductive organs (uterus and vagina). A systematic literature search using Scopus, MEDLINE via Ovid and Cochrane Library databases was conducted. Records were screened and identified for preclinical and clinical studies addressing the effects of HS on the FRS. Data on populations, interventions, outcomes and methodological quality were extracted. Studies were synthesised using tables and written summaries. Of the 198 identified records, six fulfilled the inclusion criteria. All six records were used for data extraction: two experimental studies using rats as the model organism and four human clinical studies of honey on female reproductive health. HS elevated the progesterone levels, restrained body weight increase, prevented uterine and vaginal atrophies in ovariectomised rats, attenuated symptoms of candidiasis and improved oxidative status in patients. Current evidence shows that short-term HS following surgical or physiological menopause exerts an oestrogenic, antioxidant and anti-inflammatory effect on the FRS. However, insufficient long-term studies preclude any definitive conclusions.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biological Products; Dietary Supplements; Female; Genitalia, Female; Honey; Humans; Progesterone; Uterus
PubMed: 33513715
DOI: 10.3390/molecules26030649 -
Archives of Gynecology and Obstetrics Mar 2021Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that has been used over the last decade to enhance reproductive function. The purpose... (Meta-Analysis)
Meta-Analysis
PURPOSE
Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that has been used over the last decade to enhance reproductive function. The purpose of this study is to evaluate whether PPOS is as effective as conventional protocols (without GnRHa downregulation).
METHOD
Search terms included "medroxyprogesterone", "dydrogesterone", "progestin-primed ovarian stimulation", "PPOS", "oocyte retrieval", "in vitro fertilization", "IVF", "ICSI", "ART", and "reproductive". The selection criteria were nonrandomized studies and randomized controlled studies. For data collection and analysis, the Review Manager software, Newcastle-Ottowa Quality Assessment Scale and GRADE approach were used.
RESULTS
The clinical pregnancy rates were not significantly different in either RCTs or NRCTs [RR 0.96, 95% CI (0.69-1.33), I = 71%, P = 0.81]; [RR 0.99, 95% CI (0.83-1.17), I = 38%, P = 0.88]. The live birth rates of RCTs and NRCTs did not differ [RCT: RR 1.08, 95% CI (0.74, 1.57), I = 66%, P = 0.69; NRCT: OR 1.03 95% CI 0.84-1.26), I = 50%, P = 0.79]. The PPOS protocol had a lower rate of OHSS [RR 0.52, 95% CI (0.36-0.75), I = 0%, P = 0.0006]. The secondary results showed that compared to the control protocol, the endometrium was thicker [95% CI (0.00-0.78), I = 0%, P = 0.05], the number of obtained embryos was higher [95% CI (0.04-0.65), I = 17%, P = 0.03] and more hMG was needed [in NRCT: 95% CI (307.44, 572.73), I = 0%, P < 0.00001] with the PPOS protocol.
CONCLUSION
The PPOS protocol produces more obtained embryos and a thicker endometrium than the control protocol, with a lower rate of OHSS and an equal live birth rate. The PPOS protocol could be a safe option as a personalized protocol for infertile patients.
TRIAL REGISTRATION
Registration at PROSPERO: CRD42020176577.
Topics: Dydrogesterone; Female; Fertilization in Vitro; Humans; Oocyte Retrieval; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Progestins; Reproduction
PubMed: 33433705
DOI: 10.1007/s00404-020-05939-y -
Reproductive Health Jan 2021Unintended pregnancies (UIP) have a significant impact on health of women and the health budget of countries. Contraception is an effective way to prevent UIPs. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Unintended pregnancies (UIP) have a significant impact on health of women and the health budget of countries. Contraception is an effective way to prevent UIPs. The study objective was to collate evidence on clinical effectiveness of etonogestrel subdermal implant (ESI), continuation rate and side effect profile among eligible women of reproductive age group, as compared to levonorgestrel intrauterine system (LNG-IUS), copper intrauterine device (Cu-IUD) and depot medroxy progesterone acetate injections; other types of contraceptive implants were excluded as comparators.
METHODS
The protocol of the systematic review was registered in Prospero (registration number: CRD42018116580). MEDLINE via PubMed, Cochrane library and web of science were the electronic databases searched. A search strategy was formulated and studies from 1998 to 2019 were included. Clinical trial registries and grey literature search was done. Critical assessment of included studies was done using appropriate tools. A qualitative synthesis of included studies was done and a meta-analysis was conducted in RevMan software for continuation rates of ESI as compared to other long acting reversible contraceptives (LARC) e.g. LNG IUS and Cu-IUD.
RESULTS
The search yielded 23,545 studies. After excluding 467 duplicates, 23,078 titles were screened and 51 studies were included for the review. Eight of the 15 studies reporting clinical effectiveness reported 100% effectiveness and overall pearl index ranged from 0 to 1.4. One-year continuation rates ranged from 57-97%; 44-95% at the end of second year and 25-78% by 3 years of use. Abnormal menstruation was the most commonly reported side effect. There was no significant difference in bone mineral density at 1 year follow-up. The meta-analyses showed that odds ratio (OR) of 1-year continuation rate was 1.55 (1.36, 1.76) for LNG-IUS vs. ESI and 1.34 (1.13, 1.58) for copper-IUD vs. ESI; showing that continuation rates at the end of one-year were higher in LNG-IUS and copper-IUD as compared to ESI.
CONCLUSION
ESI is clinically effective and safe contraceptive method to use, yet 1-year continuation rates are lower as compared to LNG-IUS and copper-IUD, mostly attributed to the disturbances in the menstruation.
Topics: Adolescent; Adult; Contraception Behavior; Contraceptive Agents, Female; Contraceptive Agents, Hormonal; Desogestrel; Female; Humans; Intrauterine Devices, Copper; Pregnancy; Treatment Outcome; Young Adult
PubMed: 33407632
DOI: 10.1186/s12978-020-01054-y -
Journal of Gynecology Obstetrics and... Sep 2021To systematically evaluate the effect of progestin-primed ovarian stimulation (PPOS) in in vitro fertilization (IVF)/oocyte intracytoplasmic sperm injection-embryo... (Meta-Analysis)
Meta-Analysis
PURPOSE
To systematically evaluate the effect of progestin-primed ovarian stimulation (PPOS) in in vitro fertilization (IVF)/oocyte intracytoplasmic sperm injection-embryo transfer (ICSI-ET) in patients with poor ovarian response and to find an optimal ovulation induction protocol for such patients.
METHOD
A literature search of PubMed, Medline, EBSCO, Cochrane Library, Vip.com, CNKI, and the Wanfang database was conducted to find case-control studies of PPOS with medroxyprogesterone acetate and other traditional stimulation regimens for ovulation induction in patients with poor ovarian response. The period of time searched was from the database establishment to August 2020. Patients in the experimental group underwent PPOS and those in the control group underwent another program (e.g., the gonadotropin-releasing hormone antagonist protocol). RevMan 5.3 software was used for meta-analysis.
RESULTS
A total of sixteen case-control studies (one of them is randomized controlled trial), with 4422 induction cycles, were included. All the included patients met the 2011 Bologna diagnostic criteria for poor ovarian response. The numbers of mature eggs, available embryos, optimal embryos, and the rate of cumulative pregnancies in the PPOS group were all better than those in the control group (P<0.05). There was a lower Serum luteinizing hormone on the day of human chorionic gonadotropin (HCG) injection and a lower rate of cycle cancellation in the PPOS group (P<0.05). No other differences between PPOS and other treatments were statistically significant.
CONCLUSION
PPOS can reduce the need for cycle cancellation, improve the follicles and embryos, and improve the pregnancy rate and thus, can present an effective choice for IVF/ICSI-ET in patients with poor ovarian response.
Topics: Adult; Case-Control Studies; Contraceptive Agents, Hormonal; Female; Humans; Medroxyprogesterone Acetate; Ovary; Ovulation Induction; Treatment Outcome
PubMed: 33387677
DOI: 10.1016/j.jogoh.2020.102049 -
The Cochrane Database of Systematic... Nov 2020Uterine fibroids can cause heavy menstrual bleeding. Medical treatments are considered to preserve fertility. It is unclear whether progestogens or progestogen-releasing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Uterine fibroids can cause heavy menstrual bleeding. Medical treatments are considered to preserve fertility. It is unclear whether progestogens or progestogen-releasing intrauterine systems can reduce fibroid-related symptoms. This is the first update of a Cochrane Review published in 2013.
OBJECTIVES
To determine the effectiveness of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, and PsycINFO databases to July 2020. We also searched trials registers for ongoing and registered trials, and checked references of relevant trials.
SELECTION CRITERIA
All identified published or unpublished randomised controlled trials (RCTs) assessing the effect of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data, assessed risk of bias, and assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
This updated review included four studies with 221 women with uterine fibroids. The evidence was very low quality, downgraded for serious risk of bias, due to poor reporting of study methods, and serious imprecision. Levonorgestrel-releasing intrauterine device (LNG-IUS) versus hysterectomy There was no information on the outcomes of interest, including adverse events. LNG-IUS versus low dose combined oral contraceptive (COC) At 12 months, we are uncertain whether LNG-IUS reduced the percentage of abnormal uterine bleeding, measured with the alkaline hematin test (mean difference (MD) 77.50%, 95% confidence interval (CI) 70.44 to 84.56; 1 RCT, 44 women; very low-quality evidence), or the pictorial blood assessment chart (PBAC; MD 34.50%, 95% CI 11.59 to 57.41; 1 RCT, 44 women; very low-quality evidence); increased haemoglobin levels (MD 1.50 g/dL, 95% CI 0.85 to 2.15; 1 RCT, 44 women; very low-quality evidence), or reduced fibroid size more than COC (MD 1.90%, 95% CI -12.24 to 16.04; 1 RCT, 44 women; very low-quality evidence). The study did not measure adverse events. LNG-IUS versus oral progestogen (norethisterone acetate (NETA)) Compared to NETA, we are uncertain whether LNG-IUS reduced abnormal uterine bleeding more from baseline to six months (visual bleeding score; MD 23.75 points, 95% CI 1.26 to 46.24; 1 RCT, 45 women; very low-quality evidence); increased the percentage of change in haemoglobin from baseline to three months (MD 4.53%, 95% CI 1.46 to 7.60; 1 RCT, 48 women; very low-quality evidence), or from baseline to six months (MD 10.14%, 95% CI 5.57 to 14.71; 1 RCT, 45 women; very low-quality evidence). The study did not measure fibroid size. Spotting (adverse event) was more likely to be reported by women with the LNG-IUS (64.3%) than by those taking NETA (30%; 1 RCT, 45 women; very low-quality evidence). Oral progestogen (dienogest, desogestrel) versus goserelin acetate Compared to goserelin acetate, we are uncertain whether abnormal uterine bleeding was reduced at 12 weeks with dienogest (PBAC; MD 216.00 points, 95% CI 149.35 to 282.65; 1 RCT, 14 women; very low-quality evidence) or desogestrel (PBAC; MD 78.00 points, 95% CI 28.94 to 127.06; 1 RCT, 16 women; very low-quality evidence). Vasomotor symptoms (adverse events, e.g. hot flashes) are only associated with goserelin acetate (55%), not with dienogest (1 RCT, 14 women; very low-quality evidence) or with desogestrel (1 RCT, 16 women; very low-quality evidence). The study did not report fibroid size.
AUTHORS' CONCLUSIONS
Because of very low-quality evidence, we are uncertain whether the LNG-IUS reduces abnormal uterine bleeding or increases haemoglobin levels in premenopausal women with uterine fibroids, compared to COC or norethisterone acetate. There was insufficient evidence to determine whether the LNG-IUS reduces the size of uterine fibroids compared to COC. We are uncertain whether oral progestogens reduce abnormal uterine bleeding as effectively as goserelin acetate, but women reported fewer adverse events, such as hot flashes.
Topics: Adult; Antineoplastic Agents, Hormonal; Bias; Contraceptives, Oral; Desogestrel; Female; Goserelin; Humans; Intrauterine Devices, Medicated; Leiomyoma; Leuprolide; Levonorgestrel; Lynestrenol; Medroxyprogesterone Acetate; Menstruation; Middle Aged; Nandrolone; Norethindrone Acetate; Premenopause; Progestins; Randomized Controlled Trials as Topic; Tumor Burden; Uterine Neoplasms
PubMed: 33226133
DOI: 10.1002/14651858.CD008994.pub3