-
Human Reproduction Update Jun 2021Since its introduction in the 1980s, oocyte donation (OD) has been largely integrated into ART. Lately, both demand and the indications for OD have increased greatly.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Since its introduction in the 1980s, oocyte donation (OD) has been largely integrated into ART. Lately, both demand and the indications for OD have increased greatly. Oocyte donors are healthy and potentially fertile women undergoing voluntarily ovarian stimulation (OS). Selection of the optimal type of stimulation is of paramount importance in order to achieve the most favourable outcomes for the oocyte recipients, but most importantly for the safety of the oocyte donors.
OBJECTIVE AND RATIONALE
This is the first systematic review (SR) with the objective to summarize the current evidence on OS in oocyte donors. The scope of this SR was to evaluate the OD programme by assessing four different aspects: how to assess the ovarian response prior to stimulation; how to plan the OS (gonadotrophins; LH suppression; ovulation trigger; when to start OS); how to control for the risk of ovarian hyperstimulation syndrome (OHSS) and other complications; and the differences between the use of fresh versus vitrified donated oocytes.
SEARCH METHODS
A systematic literature search was conducted in May 2020, according to PRISMA guidelines in the databases PubMed and Embase, using a string that combined synonyms for oocytes, donation, banking, freezing, complications and reproductive outcomes. Studies reporting on the safety and/or efficacy of OS in oocyte donors were identified. The quality of the included studies was assessed using ROBINS-I and ROB2. Meta-analysis was performed where appropriate. Data were combined to calculate mean differences (MD) for continuous variables and odd ratios (OR) for binary data with their corresponding 95% CIs. Heterogeneity between the included studies was assessed using I2 and tau statistics.
OUTCOMES
In total, 57 manuscripts were selected for the review, out of 191 citations identified. Antral follicle count and anti-Müllerian hormone levels correlate with ovarian response to OS in OD but have limited value to discriminate donors who are likely to show either impaired or excessive response. Five randomized controlled trials compared different type of gonadotrophins as part of OS in oocyte donors; owing to high heterogeneity, meta-analysis was precluded. When comparing different types of LH control, namely GnRH antagonist versus agonist, the studies showed no differences in ovarian response. Use of progesterone primed ovarian stimulation protocols has been evaluated in seven studies: the evidence has shown little or no difference, compared to GnRH antagonist protocols, in mean number of retrieved oocytes (MD 0.23, [95% CI 0.58-1.05], n = 2147; 6 studies; I2 = 13%, P = 0.33) and in clinical pregnancy rates among recipients (OR 0.87 [95% CI 0.60-1.26], n = 2260, I2 = 72%, P < 0.01). There is insufficient evidence on long-term safety for babies born. GnRH agonist triggering is the gold standard and should be used in all oocyte donors, given the excellent oocyte retrieval rates, the practical elimination of OHSS and no differences in pregnancy rates in recipients (four studies, OR 0.86, 95%CI 0.58-1.26; I2 = 0%). OS in OD is a safe procedure with a low rate of hospitalization after oocyte retrieval. The use of a levonorgestrel intrauterine device or a progestin contraceptive pill during OS does not impact the number of oocytes retrieved or the clinical pregnancy rate in recipients. Ultrasound monitoring seems enough for an adequate follow up of the stimulation cycle in OD. Use of fresh versus vitrified donated oocytes yielded similar pregnancy outcomes.
WIDER IMPLICATIONS
This update will be helpful in the clinical management of OS in OD based on the most recent knowledge and recommendations, and possibly in the management of women under 35 years undergoing oocyte vitrification for social freezing, owing to the population similarities. More clinical research is needed on OS protocols that are specifically designed for OD, especially in term of the long-term safety for newborns, effective contraception during OS, and treatment satisfaction.
Topics: Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infant, Newborn; Oocyte Donation; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate
PubMed: 33742206
DOI: 10.1093/humupd/dmab008 -
The Cochrane Database of Systematic... Apr 2017Uterine fibroids are smooth muscle tumours arising from the uterus. These tumours, although benign, are commonly associated with abnormal uterine bleeding, bulk symptoms... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Uterine fibroids are smooth muscle tumours arising from the uterus. These tumours, although benign, are commonly associated with abnormal uterine bleeding, bulk symptoms and reproductive dysfunction. The importance of progesterone in fibroid pathogenesis supports selective progesterone receptor modulators (SPRMs) as effective treatment. Both biochemical and clinical evidence suggests that SPRMs may reduce fibroid growth and ameliorate symptoms. SPRMs can cause unique histological changes to the endometrium that are not related to cancer, are not precancerous and have been found to be benign and reversible. This review summarises randomised trials conducted to evaluate the effectiveness of SPRMs as a class of medication for treatment of individuals with fibroids.
OBJECTIVES
To evaluate the effectiveness and safety of SPRMs for treatment of premenopausal women with uterine fibroids.
SEARCH METHODS
We searched the Specialised Register of the Cochrane Gynaecology and Fertility Group, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and clinical trials registries from database inception to May 2016. We handsearched the reference lists of relevant articles and contacted experts in the field to request additional data.
SELECTION CRITERIA
Included studies were randomised controlled trials (RCTs) of premenopausal women with fibroids who were treated for at least three months with a SPRM.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed all eligible studies identified by the search. We extracted data and assessed risk of bias independently using standard forms. We analysed data using mean differences (MDs) or standardised mean differences (SMDs) for continuous data and odds ratios (ORs) for dichotomous data. We performed meta-analyses using the random-effects model. Our primary outcome was change in fibroid-related symptoms.
MAIN RESULTS
We included in the review 14 RCTs with a total of 1215 study participants. We could not extract complete data from three studies. We included in the meta-analysis 11 studies involving 1021 study participants: 685 received SPRMs and 336 were given a control intervention (placebo or leuprolide). Investigators evaluated three SPRMs: mifepristone (five studies), ulipristal acetate (four studies) and asoprisnil (two studies). The primary outcome was change in fibroid-related symptoms (symptom severity, health-related quality of life, abnormal uterine bleeding, pelvic pain). Adverse event reporting in the included studies was limited to SPRM-associated endometrial changes. More than half (8/14) of these studies were at low risk of bias in all domains. The most common limitation of the other studies was poor reporting of methods. The main limitation for the overall quality of evidence was potential publication bias. SPRM versus placebo SPRM treatment resulted in improvements in fibroid symptom severity (MD -20.04 points, 95% confidence interval (CI) -26.63 to -13.46; four RCTs, 171 women, I = 0%; moderate-quality evidence) and health-related quality of life (MD 22.52 points, 95% CI 12.87 to 32.17; four RCTs, 200 women, I = 63%; moderate-quality evidence) on the Uterine Fibroid Symptom Quality of Life Scale (UFS-QoL, scale 0 to 100). Women treated with an SPRM showed reduced menstrual blood loss on patient-reported bleeding scales, although this effect was small (SMD -1.11, 95% CI -1.38 to -0.83; three RCTs, 310 women, I = 0%; moderate-quality evidence), along with higher rates of amenorrhoea (29 per 1000 in the placebo group vs 237 to 961 per 1000 in the SPRM group; OR 82.50, 95% CI 37.01 to 183.90; seven RCTs, 590 women, I = 0%; moderate-quality evidence), compared with those given placebo. We could draw no conclusions regarding changes in pelvic pain owing to variability in the estimates. With respect to adverse effects, SPRM-associated endometrial changes were more common after SPRM therapy than after placebo (OR 15.12, 95% CI 6.45 to 35.47; five RCTs, 405 women, I = 0%; low-quality evidence). SPRM versus leuprolide acetate In comparing SPRM versus other treatments, two RCTs evaluated SPRM versus leuprolide acetate. One RCT reported primary outcomes. No evidence suggested a difference between SPRM and leuprolide groups for improvement in quality of life, as measured by UFS-QoL fibroid symptom severity scores (MD -3.70 points, 95% CI -9.85 to 2.45; one RCT, 281 women; moderate-quality evidence) and health-related quality of life scores (MD 1.06 points, 95% CI -5.73 to 7.85; one RCT, 281 women; moderate-quality evidence). It was unclear whether results showed a difference between SPRM and leuprolide groups for reduction in menstrual blood loss based on the pictorial blood loss assessment chart (PBAC), as confidence intervals were wide (MD 6 points, 95% CI -40.95 to 50.95; one RCT, 281 women; low-quality evidence), or for rates of amenorrhoea (804 per 1000 in the placebo group vs 732 to 933 per 1000 in the SPRM group; OR 1.14, 95% CI 0.60 to 2.16; one RCT, 280 women; moderate-quality evidence). No evidence revealed differences between groups in pelvic pain scores based on the McGill Pain Questionnaire (scale 0 to 45) (MD -0.01 points, 95% CI -2.14 to 2.12; 281 women; moderate-quality evidence). With respect to adverse effects, SPRM-associated endometrial changes were more common after SPRM therapy than after leuprolide treatment (OR 10.45, 95% CI 5.38 to 20.33; 301 women; moderate-quality evidence).
AUTHORS' CONCLUSIONS
Short-term use of SPRMs resulted in improved quality of life, reduced menstrual bleeding and higher rates of amenorrhoea than were seen with placebo. Thus, SPRMs may provide effective treatment for women with symptomatic fibroids. Evidence derived from one RCT showed no difference between leuprolide acetate and SPRM with respect to improved quality of life and bleeding symptoms. Evidence was insufficient to show whether effectiveness was different between SPRMs and leuprolide. Investigators more frequently observed SPRM-associated endometrial changes in women treated with SPRMs than in those treated with placebo or leuprolide acetate. As noted above, SPRM-associated endometrial changes are benign, are not related to cancer and are not precancerous. Reporting bias may impact the conclusion of this meta-analysis. Well-designed RCTs comparing SPRMs versus other treatments are needed.
Topics: Amenorrhea; Antineoplastic Agents, Hormonal; Estrenes; Female; Humans; Leiomyoma; Leuprolide; Menstruation; Mifepristone; Norpregnadienes; Oximes; Pelvic Pain; Quality of Life; Randomized Controlled Trials as Topic; Receptors, Progesterone; Uterine Neoplasms
PubMed: 28444736
DOI: 10.1002/14651858.CD010770.pub2 -
The Cochrane Database of Systematic... 2000Endometriosis is a gynaecological condition that presents either with the problem of infertility or with painful symptoms. The clinical observation of an apparent... (Review)
Review
BACKGROUND
Endometriosis is a gynaecological condition that presents either with the problem of infertility or with painful symptoms. The clinical observation of an apparent resolution of symptoms during pregnancy gave rise to the concept of treating patients with a pseudo-pregnancy regime. Initially combinations of high dose oestrogens and progestagens were used but this was subsequently replaced by progestogens alone. More recently progestogens of both progestagens and anti-progestagens in the treatment of symptomatiprogestogenssis
OBJECTIVES
To determine the effectiveness of both the progestagens and anti-progestagens in the treatment of painful symptoms ascribed to the diagnosis of endometriosis.
SEARCH STRATEGY
The search strategy of the Menstrual Disorders and Subfertility Group was utilised to identify all publications which described or might have described randomised trials of any progestagen or any anti-progestagen in the treatment of symptomatic endometriosis.
SELECTION CRITERIA
Trials were included if they were randomised and considered the effectiveness of either a progestagen or an anti-progestagen in the treatment of painful symptoms associated with endometriosis.
DATA COLLECTION AND ANALYSIS
Seven studies were considered to be appropriate for inclusion in this review. Only three studies evaluating progestagens were included (comparison with placebo, danazol and oral contraceptive plus danazol). All other studies compared the anti-progestagen, gestrinone, with other medical therapies.
MAIN RESULTS
Progestagens appear to be an effective therapy for the painful symptoms associated with endometriosis. Gestrinone is as effective as other established medical therapies (danazol and GnRH analogues).
REVIEWER'S CONCLUSIONS
The limited available data suggests that both continuous progestagens and anti-progestagens are effective therapies in the treatment of painful symptoms associated with endometriosis. Progestagens given in the luteal phase are not effective. These conclusions should be accepted cautiously due to a lack of data.
Topics: Dydrogesterone; Endometriosis; Female; Gestrinone; Humans; Medroxyprogesterone Acetate; Pain; Progesterone Congeners; Progestins
PubMed: 10796864
DOI: 10.1002/14651858.CD002122 -
The Cochrane Database of Systematic... 2003Gonadotrophin-releasing hormone analogues (GnRHas) are generally well tolerated, and are effective in relieving the symptoms of endometriosis (Prentice 2003).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gonadotrophin-releasing hormone analogues (GnRHas) are generally well tolerated, and are effective in relieving the symptoms of endometriosis (Prentice 2003). Unfortunately the low oestrogen state that they induce is associated with adverse effects including an acceleration in bone mineral density (BMD) loss.
OBJECTIVES
To determine the effect of treatment with gonadotrophin-releasing hormone analogues (GnRHas) on the bone mineral density of women with endometriosis, compared to placebo, no treatment, or other treatments for endometriosis, including GnRHas with add-back therapy.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of controlled trials (23rd October 2002) and the Cochrane Central Register of Controlled Trials (Cochrane Library, issue 4, 2002). We also carried out electronic searches of MEDLINE (1966 - March Week 2 2003) and EMBASE (1980 - March Week 2 2003). We also searched the reference lists of articles and contacted researchers in the field.
SELECTION CRITERIA
Prospective, randomised controlled studies of the use of GnRHas for the treatment of women with endometriosis were considered, where bone density measurements were an end point. The control arm of the studies was either placebo, no treatment, another medical therapy for endometriosis, or GnRHas with add-back therapy.
DATA COLLECTION AND ANALYSIS
Two reviewers (JF and MS) independently assessed trial quality and extracted data. Study authors were contacted for additional information.
MAIN RESULTS
Thirty studies involving 2,391 women were included, however only 15, involving 910 women, could be included in the meta-analysis. The meta-analysis showed that danazol and progesterone + oestrogen add-back are protective of BMD at the lumbar spine both during treatment and for up to six and twelve months after treatment, respectively. Between the groups receiving GnRHa and the groups receiving danazol/gestrinone, there was a significant difference in percentage change of BMD after six months of treatment, the GnRH analogue producing a reduction in BMD from baseline and danazol producing an increase in BMD (SMD -3.43, 95 % CI -3.91 to -2.95). Progesterone only add-back is not protective; after six months of treatment absolute value BMD measurements of the lumbar spine did not differ significantly from the group receiving GnRH analogues (SMD 0.15, 95 % CI -0.21 to 0.52). In the comparison of GnRHa versus GnRHa + HRT add-back, that is oestrogen + progesterone or oestrogen only, there was a significantly bigger BMD loss in the GnRHa only group (SMD -0.49, 95 % CI -0.77 to -0.21). These numbers reflect the absolute value measurements at the lumbar spine after six months of treatment. Due to the small number of studies in the comparison we are unable to conclude whether calcium-regulating agents are protective. No difference was found between low and high dose add-back regimes but again only one study was identified for this comparison. Only one study comparing GnRH analogues with placebo was identified, but the study gave no data. No studies comparing GnRH with the oral contraceptive pill (OCP) or progestagens were identified.
REVIEWER'S CONCLUSIONS
Both danazol and progesterone + oestrogen add-back have been shown to be protective of BMD, while on treatment and up to six and 12 months later, respectively. However, by 24 months of follow-up there was no difference in BMD in those women who had HRT add-back. Studies of danazol versus GnRHa did not report long-term follow-up. The significant side effects associated with danazol limit its use.
Topics: Bone Density; Danazol; Endometriosis; Estrogen Antagonists; Female; Femur Neck; Gestrinone; Gonadotropin-Releasing Hormone; Humans; Lumbar Vertebrae; Manipulation, Spinal; Progesterone
PubMed: 14583930
DOI: 10.1002/14651858.CD001297 -
BJOG : An International Journal of... Jun 2008To assess the effects of aromatase inhibitors in women symptomatic of pain with endometriosis. (Review)
Review
OBJECTIVE
To assess the effects of aromatase inhibitors in women symptomatic of pain with endometriosis.
DESIGN
A systematic review of published literature.
MATERIAL AND METHODS
We conducted a comprehensive literature search to identify all the published observational and randomised studies evaluating the efficacy of aromatase inhibitors on pain associated with endometriosis. A combination of keywords was used to identify the maximum number of relevant citations in MEDLINE, EMBASE, CINAHL and the Cochrane Database. Outcome Pain relief, lesion size and quality of life.
RESULTS
There were eight studies (137 women) evaluating outcomes of aromatase inhibitors. In case series/reports (seven studies, 40 women), aromatase inhibitors combined with progestogens or oral contraceptive pill or gonadotrophin-releasing hormone (GnRH) analogues reduced mean pain scores and lesion size and improved quality of life. An RCT (97 women) demonstrated that aromatase inhibitors in combination with GnRH analogues significantly improved pain (P < 0.0001) compared with GnRH analogues alone together with significant improvement in multidimensional patient scores (P < 0.0001). There was no significant reduction in spine or hip-bone densities.
CONCLUSION
Aromatase inhibitors appear to have a promising effect on pain associated with endometriosis, but the strength of this inference is limited due to a dearth of the evidence available.
Topics: Analgesics; Angiogenesis Inhibitors; Aromatase Inhibitors; Contraceptive Agents, Female; Endometriosis; Estrogen Antagonists; Female; Humans; Immunologic Factors; Levonorgestrel; Pelvic Pain; Quality of Life; Receptors, Progesterone
PubMed: 18485158
DOI: 10.1111/j.1471-0528.2008.01740.x -
Current Problems in Cancer Dec 2020CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors are both emerging agents for hormonal receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative... (Comparative Study)
Comparative Study Meta-Analysis
Comparative efficacy and safety of CDK4/6 and PI3K/AKT/mTOR inhibitors in women with hormone receptor-positive, HER2-negative metastatic breast cancer: a systematic review and network meta-analysis.
BACKGROUND
CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors are both emerging agents for hormonal receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer. Evidence for the comparisons from head-to-head comparative trials is currently insufficient. This meta-analysis assessed the comparative efficacy and safety of these two groups of agents for HR+/HER2- metastatic breast cancer.
METHODS
Systematic searches of PubMed, Embase, CENTRAL, SciSearch between January 2010 to December 2019 were conducted. Randomized controlled trials (RCTs) which evaluated clinical benefits and toxicities of CDK4/6 inhibitors or PI3K/AKT/mTOR inhibitors plus endocrine therapy were adopted. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoint was treatment-related adverse event (TRAE). Pooled hazard ratio (HR) and risk rate (RR) were used to assess the differences between CDK4/6 and PI3K/AKT/mTOR inhibitors.
RESULTS
A total of twenty RCTs including 9771 participants were identified in this study. Pooled results showed that PFS was considerably prolonged by targeted therapy plus endocrine therapy. PFS was relatively better in CDK4/6 inhibitors than that of PI3K inhibitor group (HR, 1.43; 95%CrI, 1.12-1.61). Similar results were demonstrated in results after balancing lines of therapy or metastatic sites, both in viscera and bone-only. Coalesced outcomes revealed that CDK4/6 inhibitors plus endocrine therapy could significantly improve OS (HR, 0.78; 95%CrI, 0.65-0.94) than PI3K/mTOR inhibitors. Safety profiles of diarrhea and rash were consistent between CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors with no difference of estimated RR. Several TRAEs signified specificity, for instance, myelosuppression in CDK4/6 inhibitors or hyperglycemia in PI3K/mTOR inhibitors.
CONCLUSIONS
Clinical efficacy is in favor of CDK4/6 inhibitors, and safety profiles are comparable between CDK4/6 inhibitors or PI3K/AKT/mTOR inhibitors plus endocrine therapy.
Topics: Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Humans; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; TOR Serine-Threonine Kinases
PubMed: 32446638
DOI: 10.1016/j.currproblcancer.2020.100606 -
Contraception Feb 2005Male hormonal contraception has been an elusive goal. Administration of sex steroids to men can shut off sperm production through effects on the pituitary and... (Meta-Analysis)
Meta-Analysis Review
Male hormonal contraception has been an elusive goal. Administration of sex steroids to men can shut off sperm production through effects on the pituitary and hypothalamus. However, this approach also decreases production of testosterone, so an "add-back" therapy is needed. We conducted a systematic review of all randomized controlled trials of male hormonal contraception and azoospermia. Few significant differences emerged from these trials. Levonorgestrel implants combined with injectable testosterone enanthate (100 mg im) were significantly more effective than was levonorgestrel 125 microg po daily combined with testosterone patches [10 mg/d; odds ratio (OR) for azoospermia with the oral levonorgestrel regimen, 0.03; 95% CI, 0.00-0.29]. The addition of levonorgestrel 500 microg po daily improved the effectiveness of testosterone enanthate 100 mg im weekly by itself (OR for azoospermia with the combined regimen, 4.0; 95% CI, 1.00-15.99). Several regimens, including testosterone alone and gonadotropin-releasing hormone agonists and antagonists, had disappointing results. In conclusion, no male hormonal contraceptive is ready for clinical use. All trials published to date have been small exploratory studies. As a result, their power to detect important differences has been limited and their results have been imprecise. In addition, the definition of oligospermia has been imprecise or inconsistent in many reports. To avoid bias, future trials need to pay more attention on the methodological requirements for randomized controlled trials. Trials with adequate power would also be helpful.
Topics: Adult; Contraception; Contraceptives, Oral, Synthetic; Desogestrel; Gonadal Steroid Hormones; Humans; Male; Oligospermia; Progesterone Congeners; Randomized Controlled Trials as Topic; Testosterone; Treatment Outcome
PubMed: 15707556
DOI: 10.1016/j.contraception.2004.10.001 -
Fertility and Sterility Dec 2008To investigate the effect of luteal E(2) supplementation on the pregnancy rate of IVF/intracytoplasmic sperm injection (ICSI) cycles. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate the effect of luteal E(2) supplementation on the pregnancy rate of IVF/intracytoplasmic sperm injection (ICSI) cycles.
DESIGN
A systematic review and meta-analysis of all the randomized controlled trials (RCTs).
SETTING
Tertiary referral center for reproductive medicine and IVF.
PATIENT(S)
Women undergoing IVF or ICSI using the GnRH agonist or GnRH antagonist protocol with hMG or FSH for controlled ovarian hyperstimulation.
INTERVENTION(S)
Progesterone (P4) alone or combined with estradiol valerate for luteal phase support.
MAIN OUTCOME MEASURE(S)
Pregnancy and clinical pregnancy rates per ET.
RESULT(S)
An electronic search was conducted targeting all reports published between January 1960 and March 2007. Ten RCTs met the criteria for inclusion in the meta-analysis. There were no statistically significant differences with regard to the main outcome measures, ongoing pregnancy rate per ET, or implantation rate between the group of women who had combined E(2) and P4 therapy and those who had P4 supplementation alone.
CONCLUSION(S)
The addition of E(2) to P4 for luteal phase support in IVF/ICSI cycles has no beneficial effect on pregnancy rates. The data in the literature are, however, limited and heterogeneous, precluding the extraction of clear and definite conclusions. A large multicenter, properly designed RCT is needed to further clarify the role of luteal E(2) supplementation in IVF.
Topics: Adult; Drug Therapy, Combination; Embryo Implantation; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Infertility; Luteal Phase; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Sperm Injections, Intracytoplasmic; Treatment Outcome
PubMed: 18178194
DOI: 10.1016/j.fertnstert.2007.10.053 -
The Cochrane Database of Systematic... Jul 2014Preterm birth represents the single largest cause of mortality and morbidity for newborns and a major cause of morbidity for pregnant women. Tocolytic agents include a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preterm birth represents the single largest cause of mortality and morbidity for newborns and a major cause of morbidity for pregnant women. Tocolytic agents include a wide range of drugs that can inhibit labour to prolong pregnancy. This may gain time to allow the fetus to mature further before being born, permit antenatal corticosteroid administration for lung maturation, and allow time for intra-uterine transfer to a hospital with neonatal intensive care facilities. However, some tocolytic drugs are associated with severe side effects. Combinations of tocolytic drugs may be more effective over single tocolytic agents or no intervention, without adversely affecting the mother or neonate.
OBJECTIVES
To assess the effects on maternal, fetal and neonatal outcomes of any combination of tocolytic drugs for the treatment of preterm labour when compared with any other treatment, no treatment or placebo.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2014) and reference lists of retrieved studies.
SELECTION CRITERIA
We included randomised controlled trials comparing a combination of tocolytic agents, administered by any route or any dose, for inhibiting preterm labour versus any other treatment (including other combinations of tocolytics or single tocolytics), no intervention or placebo.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study reports for eligibility, carried out data extraction and assessed risk of bias.
MAIN RESULTS
Eleven studies met our inclusion criteria. Two studies did not report any outcome data relevant to the review, so the results of the review are based on nine trials that contributed data. Primary outcomes were perinatal mortality, serious maternal or infant outcomes, adverse drug reactions, birth before 48 hours of trial entry, birth before 34 weeks' gestation and preterm neonates delivered without a full course of antenatal steroids completed 24 hours before birth. The quality of evidence in included trials was mixed; only three of the trials were placebo controlled.The included trials examined seven different comparisons: intravenous (IV) ritodrine plus oral or IV magnesium (sulphate or gluconate) versus IV ritodrine alone (three trials, 231 women); IV ritodrine plus indomethacin suppositories versus IV ritodrine alone (one trial, 208 women); IV ritodrine plus vaginal progesterone versus IV ritodrine alone (one trial, 83 women); IV hexoprenaline sulphate plus IV magnesium hydrochloride versus IV hexoprenaline sulphate alone (one trial, 24 women); IV fenoterol plus oral naproxen versus IV fenoterol alone (one trial, 72 women); oral pentoxifylline plus IV magnesium sulphate plus IV fenoterol versus IV magnesium sulphate plus IV fenoterol (one trial, 125 women); and, IV terbutaline plus oral metoprolol versus IV terbutaline alone (one trial, 17 women). Few studies with small numbers of women were available for each comparison, hence very little data were pooled in meta-analysis. In all trials, not many of the primary outcomes were reported.Three trials examined intravenous (IV) ritodrine plus IV or oral magnesium (sulphate or gluconate) compared with IV ritodrine alone. One study, with 41 women, reported more adverse drug reactions in the group receiving the combined tocolytics (risk ratio (RR) 7.79, 95% confidence interval (CI) 1.11 to 54.80). Two trials reported discontinuation of therapy due to severe side effects (results were not combined due to high statistical heterogeneity, I² = 83%); one trial reported increased severe side effects in the group receiving IV ritodrine alone (RR 7.79, 95% CI 1.11 to 54.80, 41 women); in the other trial there was no clear difference between groups (RR 0.23, 95% CI 0.03 to 1.97, 107 women). Other primary outcomes were not reported.One trial assessed IV ritodrine plus indomethacin suppositories versus IV ritodrine alone. There were no significant differences between groups for perinatal mortality or serious neonatal morbidity. Results for other primary outcomes were not reported.There were no significant differences between groups receiving IV ritodrine plus vaginal progesterone compared with IV ritodrine alone for most outcomes reported, although the latency period (time from recruitment to delivery) was increased in the group receiving the combination of tocolytics.For other combinations of tocolytic agents, primary outcomes were rarely reported and for secondary outcomes results did not demonstrate differences between groups.
AUTHORS' CONCLUSIONS
It is unclear whether a combination of tocolytic drugs for preterm labour is more advantageous for women and/or newborns due to a lack of large, well-designed trials including the outcomes of interest. There are no trials of combination regimens using widely used tocolytic agents, such as calcium channel blockers (nifedipine) and/or oxytocin receptor antagonists (atosiban). Further trials are needed before specific conclusions on use of combination tocolytic therapy for preterm labour can be made.
Topics: Drug Therapy, Combination; Female; Humans; Infant, Newborn; Obstetric Labor, Premature; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Tocolysis; Tocolytic Agents
PubMed: 25010869
DOI: 10.1002/14651858.CD006169.pub2 -
Cancer Investigation May 2021To evaluate the efficacy and safety of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors combined with endocrine therapy (ET) for hormone receptor-positive (HR+)/human... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors combined with endocrine therapy (ET) for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER-2-) advanced breast cancer (ABC) patients.
METHODS
We searched clinical trials of CDK4/6 inhibitors combined with ET and calculated the clinical outcomes.
RESULTS
HR+/HER-2- ABC patients treated with CDK4/6 inhibitors combined with ET had significantly prolonged progression-free survival (PFS) and improved objective response rate (ORR) and clinical benefit rate (CBR).
CONCLUSIONS
CDK4/6 inhibitors combined with ET can bring more clinical benefits to ABC patients, and the safety profile is acceptable.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Humans; Receptors, Estrogen; Receptors, Progesterone
PubMed: 33886387
DOI: 10.1080/07357907.2021.1910705