-
Thyroid : Official Journal of the... Apr 2016The impact of subclinical hypothyroidism (SCH) and of levothyroxine replacement in pregnant women with SCH is unclear. The aims of this study were to assess (i) the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The impact of subclinical hypothyroidism (SCH) and of levothyroxine replacement in pregnant women with SCH is unclear. The aims of this study were to assess (i) the impact of SCH during pregnancy on maternal and neonatal outcomes, and (ii) the effect of levothyroxine replacement therapy in these patients.
METHODS
Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, the Cochrane Controlled Trials Register, Ovid EMBASE, Web of Science, and Scopus were searched from inception to January 2015. Randomized trials and cohort studies of pregnant women with SCH that examined adverse pregnancy and neonatal outcomes were included. Reviewers extracted data and assessed methodological quality in duplicate. Eighteen cohort studies at low-to-moderate risk of bias were included. Compared with euthyroid pregnant women, pregnant women with SCH were at higher risk for pregnancy loss (relative risk [RR] 2.01 [confidence interval (CI) 1.66-2.44]), placental abruption (RR 2.14 [CI 1.23-3.70]), premature rupture of membranes (RR 1.43 [CI 1.04-1.95]), and neonatal death (RR 2.58 [CI 1.41-4.73]). One study at high risk of bias compared pregnant women with SCH who received levothyroxine to those who did not and found no significant decrease in the rate of pregnancy loss, preterm delivery, gestational hypertension, low birth weight, or low Apgar score.
CONCLUSIONS
SCH during pregnancy is associated with multiple adverse maternal and neonatal outcomes. The value of levothyroxine therapy in preventing these adverse outcomes remains uncertain.
Topics: Abortion, Spontaneous; Female; Humans; Hypothyroidism; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Risk Assessment; Thyroxine; Treatment Outcome
PubMed: 26837268
DOI: 10.1089/thy.2015.0418 -
Human Reproduction Update Mar 2019Early reproductive failure is the most common complication of pregnancy with only 30% of conceptions reaching live birth. Establishing a successful pregnancy depends... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early reproductive failure is the most common complication of pregnancy with only 30% of conceptions reaching live birth. Establishing a successful pregnancy depends upon implantation, a complex process involving interactions between the endometrium and the blastocyst. It is estimated that embryos account for one-third of implantation failures, while suboptimal endometrial receptivity and altered embryo-endometrial dialogue are responsible for the remaining two-thirds. Endometrial receptivity has been the focus of extensive research for over 80 years, leading to an indepth understanding of the processes associated with embryo-endometrial cross-talk and implantation. However, little progress has been achieved to translate this understanding into clinically meaningful prognostic tests and treatments for suboptimal endometrial receptivity.
OBJECTIVE AND RATIONALE
The objective of this systematic review was to examine the evidence from observational studies supporting the use of endometrial receptivity markers as prognostic factors for pregnancy outcome in women wishing to conceive, in order to aid clinicians in choosing the most useful marker in clinical practice and for informing further research.
SEARCH METHODS
The review protocol was registered with PROSPERO (CRD42017077891). MEDLINE and Embase were searched for observational studies published from inception until 26 February 2018. We included studies that measured potential markers of endometrial receptivity prior to pregnancy attempts and reported the subsequent pregnancy outcomes. We performed association and accuracy analyses using clinical pregnancy as an outcome to reflect the presence of receptive endometrium. The Newcastle-Ottawa scale for observational studies was employed to assess the quality of the included studies.
OUTCOMES
We included 163 studies (88 834 women) of moderate overall quality in the narrative synthesis, out of which 96 were included in the meta-analyses. Studies reported on various endometrial receptivity markers evaluated by ultrasound, endometrial biopsy, endometrial fluid aspirate and hysteroscopy in the context of natural conception, IUI and IVF. Associations were identified between clinical pregnancy and various endometrial receptivity markers (endometrial thickness, endometrial pattern, Doppler indices, endometrial wave-like activity and various molecules); however, their poor ability to predict clinical pregnancy prevents them from being used in clinical practice. Results from several modern molecular tests are promising and further data are awaited.
WIDER IMPLICATIONS
The post-test probabilities from our analyses may be used in clinical practice to manage couples' expectations during fertility treatments (IUI and IVF). Conventionally, endometrial receptivity is seen as a dichotomous outcome (present or absent), but we propose that various levels of endometrial receptivity exist within the window of implantation. For instance, different transcriptomic signatures could represent varying levels of endometrial receptivity, which can be linked to different pregnancy outcomes. Many studies reported the means of a particular biomarker in those who achieved a pregnancy compared with those who did not. However, extreme values of a biomarker (as opposite to the means) may have significant prognostic and diagnostic implications that are not captured in the means. Therefore, we suggest reporting the outcomes by categories of biomarker levels rather than reporting means of biomarker levels within clinical outcome groups.
Topics: Biomarkers; Embryo Implantation; Endometrium; Female; Fertility; Fertilization in Vitro; Humans; Hysteroscopy; Live Birth; Observational Studies as Topic; Pregnancy; Pregnancy, Multiple
PubMed: 30624659
DOI: 10.1093/humupd/dmy044 -
The Cochrane Database of Systematic... May 2022Advances in embryo culture media have led to a shift in in vitro fertilisation (IVF) practice from cleavage-stage embryo transfer to blastocyst-stage embryo transfer.... (Review)
Review
BACKGROUND
Advances in embryo culture media have led to a shift in in vitro fertilisation (IVF) practice from cleavage-stage embryo transfer to blastocyst-stage embryo transfer. The rationale for blastocyst-stage transfer is to improve both uterine and embryonic synchronicity and enable self selection of viable embryos, thus resulting in better live birth rates.
OBJECTIVES
To determine whether blastocyst-stage (day 5 to 6) embryo transfer improves the live birth rate (LBR) per fresh transfer, and other associated outcomes, compared with cleavage-stage (day 2 to 3) embryo transfer.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL, from inception to October 2021. We also searched registers of ongoing trials and the reference lists of studies retrieved.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) which compared the effectiveness of IVF with blastocyst-stage embryo transfer versus IVF with cleavage-stage embryo transfer.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. Our primary outcomes were LBR per fresh transfer and cumulative clinical pregnancy rates (cCPR). Secondary outcomes were clinical pregnancy rate (CPR), multiple pregnancy, high-order multiple pregnancy, miscarriage (all following first embryo transfer), failure to transfer embryos, and whether supernumerary embryos were frozen for transfer at a later date (frozen-thawed embryo transfer). We assessed the overall quality of the evidence for the main comparisons using GRADE methods.
MAIN RESULTS
We included 32 RCTs (5821 couples or women). The live birth rate following fresh transfer was higher in the blastocyst-stage transfer group (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06 to 1.51; I = 53%; 15 studies, 2219 women; low-quality evidence). This suggests that if 31% of women achieve live birth after fresh cleavage-stage transfer, between 32% and 41% would do so after fresh blastocyst-stage transfer. We are uncertain whether blastocyst-stage transfer improves the cCPR. A post hoc analysis showed that vitrification could increase the cCPR. This is an interesting finding that warrants further investigation when more studies using vitrification are published. The CPR was also higher in the blastocyst-stage transfer group, following fresh transfer (OR 1.25, 95% CI 1.12 to 1.39; I = 51%; 32 studies, 5821 women; moderate-quality evidence). This suggests that if 39% of women achieve a clinical pregnancy after fresh cleavage-stage transfer, between 42% and 47% will probably do so after fresh blastocyst-stage transfer. We are uncertain whether blastocyst-stage transfer increases multiple pregnancy (OR 1.05, 95% CI 0.83 to 1.33; I = 30%; 19 studies, 3019 women; low-quality evidence) or miscarriage rates (OR 1.12, 95% CI 0.90 to 1.38; I = 24%; 22 studies, 4208 women; low-quality evidence). This suggests that if 9% of women have a multiple pregnancy after fresh cleavage-stage transfer, between 8% and 12% would do so after fresh blastocyst-stage transfer. However, a sensitivity analysis restricted only to studies with low or 'some concerns' for risk of bias, in the subgroup of equal number of embryos transferred, showed that blastocyst transfer probably increases the multiple pregnancy rate. Embryo freezing rates (when there are frozen supernumerary embryos for transfer at a later date) were lower in the blastocyst-stage transfer group (OR 0.48, 95% CI 0.40 to 0.57; I = 84%; 14 studies, 2292 women; low-quality evidence). This suggests that if 60% of women have embryos frozen after cleavage-stage transfer, between 37% and 46% would do so after blastocyst-stage transfer. Failure to transfer any embryos was higher in the blastocyst transfer group (OR 2.50, 95% CI 1.76 to 3.55; I = 36%; 17 studies, 2577 women; moderate-quality evidence). This suggests that if 1% of women have no embryos transferred in planned fresh cleavage-stage transfer, between 2% and 4% probably have no embryos transferred in planned fresh blastocyst-stage transfer. The evidence was of low quality for most outcomes. The main limitations were serious imprecision and serious risk of bias, associated with failure to describe acceptable methods of randomisation.
AUTHORS' CONCLUSIONS
There is low-quality evidence for live birth and moderate-quality evidence for clinical pregnancy that fresh blastocyst-stage transfer is associated with higher rates of both than fresh cleavage-stage transfer. We are uncertain whether blastocyst-stage transfer improves the cCPR derived from fresh and frozen-thawed cycles following a single oocyte retrieval. Although there is a benefit favouring blastocyst-stage transfer in fresh cycles, more evidence is needed to know whether the stage of transfer impacts on cumulative live birth and pregnancy rates. Future RCTs should report rates of live birth, cumulative live birth, and miscarriage. They should also evaluate women with a poor prognosis to enable those undergoing assisted reproductive technology (ART) and service providers to make well-informed decisions on the best treatment option available.
Topics: Abortion, Spontaneous; Blastocyst; Embryo Transfer; Female; Humans; Live Birth; Pregnancy; Pregnancy Rate; Reproductive Techniques, Assisted
PubMed: 35588094
DOI: 10.1002/14651858.CD002118.pub6 -
Frontiers in Public Health 2022Anemia in pregnancy is a serious threat to maternal and child health and is a major public health problem. However, the risk factors associated with its incidence are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anemia in pregnancy is a serious threat to maternal and child health and is a major public health problem. However, the risk factors associated with its incidence are unclear and controversial.
METHODS
PubMed, Ovid Embase, Web of Science, and Cochrane databases were systematically searched (inception to June 27, 2022). The screening of search results, extraction of relevant data, and evaluation of study quality were performed independently by two reviewers.
RESULTS
A total of 51 studies of high quality (NOS score ≥ 7) were included, including 42 cross-sectional studies, six case-control studies, and three cohort studies. Meta-analysis showed that infected parasite, history of malarial attack, tea/coffee after meals, meal frequency ≤ 2 times per day, frequency of eating meat ≤ 1 time per week, frequency of eating vegetables ≤ 3 times per week, multiple pregnancies, multiparous, low household income, no antenatal care, rural residence, diet diversity score ≤ 3, have more than 3 children, history of menorrhagia, underweight, family size ≥ 5, middle upper arm circumference < 23, second trimester, third trimester, birth interval ≤ 2 year were all risk factors for anemia in pregnancy.
CONCLUSIONS
Prevention of anemia in pregnancy is essential to promote maternal and child health. Sufficient attention should be paid to the above risk factors from the social level and pregnant women's own aspects to reduce the occurrence of anemia in pregnancy.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42022344937.
Topics: Child; Pregnancy; Female; Humans; Cross-Sectional Studies; Anemia; Prenatal Care; Cohort Studies; Risk Factors
PubMed: 36311562
DOI: 10.3389/fpubh.2022.1041136 -
Archives of Gynecology and Obstetrics Jul 2021In December 2019, a novel coronavirus disease (COVID-19) emerged in Wuhan, China, with an incredible contagion rate. However, the vertical transmission of COVID-19 is... (Review)
Review
BACKGROUND
In December 2019, a novel coronavirus disease (COVID-19) emerged in Wuhan, China, with an incredible contagion rate. However, the vertical transmission of COVID-19 is uncertain.
OBJECTIVES
This is a systematic review of published studies concerning pregnant women with confirmed COVID-19 and their neonates.
SEARCH STRATEGY
We carried out a systematic search in multiple databases, including PubMed, Web of Science, Google Scholar, Scopus, and WHO COVID-19 database using the following keywords: (Coronavirus) OR (novel coronavirus) OR (COVID-19) OR (COVID19) OR (COVID 19) OR (SARS-CoV2) OR (2019-nCoV)) and ((pregnancy) OR (pregnant) OR (vertical transmission) OR (neonate) OR (newborn) OR (placenta) OR (fetus) OR (Fetal)). The search took place in April 2020.
SELECTION CRITERIA
Original articles published in English were eligible if they included pregnant patients infected with COVID-19 and their newborns.
DATA COLLECTION AND ANALYSES
The outcomes of interest consisted of clinical manifestations of COVID-19 in pregnant patients with COVID-19 and also the effect of COVID-19 on neonatal and pregnancy outcomes.
MAIN RESULTS
37 articles involving 364 pregnant women with COVID-19 and 302 neonates were included. The vast majority of pregnant patients were in their third trimester of pregnancy, and only 45 cases were in the first or second trimester (12.4%). Most mothers described mild to moderate manifestations of COVID-19. Of 364 pregnant women, 25 were asymptomatic at the time of admission. The most common symptoms were fever (62.4%) and cough (45.3%). Two maternal deaths occurred. Some pregnant patients (12.1%) had a negative SARS-CoV-2 test but displayed clinical manifestations and abnormalities in computed tomography (CT) scan related to COVID-19. Twenty-two (6.0%) pregnant patients developed severe pneumonia. Two maternal deaths occurred from severe pneumonia and multiple organ dysfunction. Studies included a total of 302 neonates from mothers with COVID-19. Of the studies that provided data on the timing of birth, there were 65 (23.6%) preterm neonates. One baby was born dead from a mother who also died from COVID-19. Of the babies born alive from mothers with COVID-19, five newborns faced critical conditions, and two later died. A total of 219 neonates underwent nasopharyngeal specimen collection for SARS-CoV-2, of which 11 tested positive (5%). Seventeen studies examined samples of the placenta, breast milk, umbilical cord, and amniotic fluid, and all tested negative except one amniotic fluid sample.
CONCLUSIONS
A systematic review of published studies confirm that the course of COVID-19 in pregnant women resembles that of other populations. However, there is not sufficient evidence to establish an idea that COVID-19 would not complicate pregnancy.
Topics: Adult; Amniotic Fluid; COVID-19; Female; Fever; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Mothers; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Pregnancy Trimester, Third; Pregnant Women; RNA, Viral; SARS-CoV-2
PubMed: 33797605
DOI: 10.1007/s00404-021-06049-z -
Reproductive Health Sep 2014There is increasingly a double burden of under-nutrition and obesity in women of reproductive age. Preconception underweight or overweight, short stature and... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
There is increasingly a double burden of under-nutrition and obesity in women of reproductive age. Preconception underweight or overweight, short stature and micronutrient deficiencies all contribute to excess maternal and fetal complications during pregnancy.
METHODS
A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on maternal, newborn and child health (MNCH) outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture.
RESULTS
Maternal pre-pregnancy weight is a significant factor in the preconception period with underweight contributing to a 32% higher risk of preterm birth, and obesity more than doubling the risk for preeclampsia, gestational diabetes. Overweight women are more likely to undergo a Cesarean delivery, and their newborns have higher chances of being born with a neural tube or congenital heart defect. Among nutrition-specific interventions, preconception folic acid supplementation has the strongest evidence of effect, preventing 69% of recurrent neural tube defects. Multiple micronutrient supplementation shows promise to reduce the rates of congenital anomalies and risk of preeclampsia. Although over 40% of women worldwide are anemic in the preconception period, only one study has shown a risk for low birth weight.
CONCLUSION
All women, but especially those who become pregnant in adolescence or have closely-spaced pregnancies (inter-pregnancy interval less than six months), require nutritional assessment and appropriate intervention in the preconception period with an emphasis on optimizing maternal body mass index and micronutrient reserves. Increasing coverage of nutrition-specific and nutrition-sensitive strategies (such as food fortification; integration of nutrition initiatives with other maternal and child health interventions; and community based platforms) is necessary among adolescent girls and women of reproductive age. The effectiveness of interventions will need to be simultaneously monitored, and form the basis for the development of improved delivery strategies and new nutritional interventions.
Topics: Body Weight; Congenital Abnormalities; Dietary Supplements; Female; Folic Acid; Humans; Infant, Newborn; Preconception Care; Pregnancy; Pregnancy Complications; Prenatal Nutritional Physiological Phenomena
PubMed: 25415364
DOI: 10.1186/1742-4755-11-S3-S3 -
BMJ (Clinical Research Ed.) Nov 2020To assess whether exposure to high temperatures in pregnancy is associated with increased risk for preterm birth, low birth weight, and stillbirth. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess whether exposure to high temperatures in pregnancy is associated with increased risk for preterm birth, low birth weight, and stillbirth.
DESIGN
Systematic review and random effects meta-analysis.
DATA SOURCES
Medline and Web of Science searched up to September 2018, updated in August 2019.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Clinical studies on associations between high environmental temperatures, and preterm birth, birth weight, and stillbirths.
RESULTS
14 880 records and 175 full text articles were screened. 70 studies were included, set in 27 countries, seven of which were countries with low or middle income. In 40 of 47 studies, preterm births were more common at higher than lower temperatures. Exposures were classified as heatwaves, 1°C increments, and temperature threshold cutoff points. In random effects meta-analysis, odds of a preterm birth rose 1.05-fold (95% confidence interval 1.03 to 1.07) per 1°C increase in temperature and 1.16-fold (1.10 to 1.23) during heatwaves. Higher temperature was associated with reduced birth weight in 18 of 28 studies, with considerable statistical heterogeneity. Eight studies on stillbirths all showed associations between temperature and stillbirth, with stillbirths increasing 1.05-fold (1.01 to 1.08) per 1°C rise in temperature. Associations between temperature and outcomes were largest among women in lower socioeconomic groups and at age extremes. The multiple temperature metrics and lag analyses limited comparison between studies and settings.
CONCLUSIONS
Although summary effect sizes are relatively small, heat exposures are common and the outcomes are important determinants of population health. Linkages between socioeconomic status and study outcomes suggest that risks might be largest in low and middle income countries. Temperature rises with global warming could have major implications for child health.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD 42019140136 and CRD 42018118113.
Topics: Female; Hot Temperature; Humans; Infant, Low Birth Weight; Infant, Newborn; Pregnancy; Premature Birth; Risk Factors; Stillbirth
PubMed: 33148618
DOI: 10.1136/bmj.m3811 -
Nutrients Feb 2020Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during... (Meta-Analysis)
Meta-Analysis
Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.
Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included. Meta-analyses showed improvement in several key birth outcomes, such as preterm birth, small-for-gestational age (SGA) and low birthweight with MMN supplementation, compared to IFA. MMN also improved child outcomes, including diarrhea incidence and retinol concentration, which are findings not previously reported. Across all comparisons, micronutrient supplementation had little to no effect on mortality (maternal, neonatal, perinatal, and infant) outcomes, which is consistent with other systematic reviews. IFA supplementation showed notable improvement in maternal anemia and the reduction in low birthweight, whereas LNS supplementation had no apparent effect on outcomes; further research that compares LNS and MMN supplementation could help understand differences with these commodities. For single micronutrient supplementation, improvements were noted in only a few outcomes, mainly pre-eclampsia/eclampsia (calcium), maternal anemia (iron), preterm births (vitamin D), and maternal serum zinc concentration (zinc). These findings highlight that micronutrient-specific supplementation should be tailored to specific groups or needs for maximum benefit. In addition, they further contribute to the ongoing discourse of choosing antenatal MMN over IFA as the standard of care in LMICs.
Topics: Anemia; Child; Child Development; Child, Preschool; Developing Countries; Dietary Supplements; Female; Humans; Income; Infant; Maternal Nutritional Physiological Phenomena; Micronutrients; Minerals; Poverty Areas; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Randomized Controlled Trials as Topic; Vitamins
PubMed: 32075071
DOI: 10.3390/nu12020491 -
The Cochrane Database of Systematic... Jul 2017Among subfertile couples undergoing assisted reproductive technology (ART), pregnancy rates following frozen-thawed embryo transfer (FET) treatment cycles have... (Meta-Analysis)
Meta-Analysis Review
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, I = 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.
Topics: Clomiphene; Cryopreservation; Embryo Transfer; Endometrium; Estrogens; Female; Fertility Agents, Female; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Randomized Controlled Trials as Topic
PubMed: 28675921
DOI: 10.1002/14651858.CD003414.pub3 -
Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.The Cochrane Database of Systematic... Mar 2017Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. While researching the effects of the steroid dexamethasone on premature parturition in fetal sheep in 1969, Liggins found that there was some inflation of the lungs of lambs born at gestations at which the lungs would be expected to be airless. Liggins and Howie published the first randomised controlled trial in humans in 1972 and many others followed.
OBJECTIVES
To assess the effects of administering a course of corticosteroids to the mother prior to anticipated preterm birth on fetal and neonatal morbidity and mortality, maternal mortality and morbidity, and on the child in later life.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (17 February 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
We considered all randomised controlled comparisons of antenatal corticosteroid administration (betamethasone, dexamethasone, or hydrocortisone) with placebo, or with no treatment, given to women with a singleton or multiple pregnancy, prior to anticipated preterm delivery (elective, or following spontaneous labour), regardless of other co-morbidity, for inclusion in this review. Most women in this review received a single course of steroids; however, nine of the included trials allowed for women to have weekly repeats.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach.
MAIN RESULTS
This update includes 30 studies (7774 women and 8158 infants). Most studies are of low or unclear risk for most bias domains. An assessment of high risk usually meant a trial had potential for performance bias due to lack of blinding. Two trials had low risks of bias for all risk of bias domains.Treatment with antenatal corticosteroids (compared with placebo or no treatment) is associated with a reduction in the most serious adverse outcomes related to prematurity, including: perinatal death (average risk ratio (RR) 0.72, 95% confidence interval (CI) 0.58 to 0.89; participants = 6729; studies = 15; Tau² = 0.05, I² = 34%; moderate-quality); neonatal death (RR 0.69, 95% CI 0.59 to 0.81; participants = 7188; studies = 22), RDS (average RR 0.66, 95% CI 0.56 to 0.77; participants = 7764; studies = 28; Tau² = 0.06, I² = 48%; moderate-quality); moderate/severe RDS (average RR 0.59, 95% CI 0.38 to 0.91; participants = 1686; studies = 6; Tau² = 0.14, I² = 52%); intraventricular haemorrhage (IVH) (average RR 0.55, 95% CI 0.40 to 0.76; participants = 6093; studies = 16; Tau² = 0.10, I² = 33%; moderate-quality), necrotising enterocolitis (RR 0.50, 95% CI 0.32 to 0.78; participants = 4702; studies = 10); need for mechanical ventilation (RR 0.68, 95% CI 0.56 to 0.84; participants = 1368; studies = 9); and systemic infections in the first 48 hours of life (RR 0.60, 95% CI 0.41 to 0.88; participants = 1753; studies = 8).There was no obvious benefit for: chronic lung disease (average RR 0.86, 95% CI 0.42 to 1.79; participants = 818; studies = 6; Tau² = 0.38 I² = 65%); mean birthweight (g) (MD -18.47, 95% CI -40.83 to 3.90; participants = 6182; studies = 16; moderate-quality); death in childhood (RR 0.68, 95% CI 0.36 to 1.27; participants = 1010; studies = 4); neurodevelopment delay in childhood (RR 0.64, 95% CI 0.14 to 2.98; participants = 82; studies = 1); or death into adulthood (RR 1.00, 95% CI 0.56 to 1.81; participants = 988; studies = 1).Treatment with antenatal corticosteroids does not increase the risk of chorioamnionitis (RR 0.83, 95% CI 0.66 to 1.06; participants = 5546; studies = 15; moderate-quality evidence) or endometritis (RR 1.20, 95% CI 0.87 to 1.63; participants = 4030; studies = 10; Tau² = 0.11, I² = 28%; moderate-quality). No increased risk in maternal death was observed. However, the data on maternal death is based on data from a single trial with two deaths; four other trials reporting maternal death had zero events (participants = 3392; studies = 5; moderate-quality).There is no definitive evidence to suggest that antenatal corticosteroids work differently in any pre-specified subgroups (singleton versus multiple pregnancy; membrane status; presence of hypertension) or for different study protocols (type of corticosteroid; single course or weekly repeats).GRADE outcomes were downgraded to moderate-quality. Downgrading decisions (for perinatal death, RDS, IVH, and mean birthweight) were due to limitations in study design or concerns regarding precision (chorioamnionitis, endometritis). Maternal death was downgraded for imprecision due to few events.
AUTHORS' CONCLUSIONS
Evidence from this update supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. A single course of antenatal corticosteroids could be considered routine for preterm delivery. It is important to note that most of the evidence comes from high income countries and hospital settings; therefore, the results may not be applicable to low-resource settings with high rates of infections.There is little need for further trials of a single course of antenatal corticosteroids versus placebo in singleton pregnancies in higher income countries and hospital settings. However, data are sparse in lower income settings. There are also few data regarding risks and benefits of antenatal corticosteroids in multiple pregnancies and other high-risk obstetric groups. Further information is also required concerning the optimal dose-to-delivery interval, and the optimal corticosteroid to use.We encourage authors of previous studies to provide further information, which may answer any remaining questions about the use of antenatal corticosteroids in such pregnancies without the need for further randomised controlled trials. Individual patient data meta-analysis from published trials is likely to answer some of the evidence gaps. Follow-up studies into childhood and adulthood, particularly in the late preterm gestation and repeat courses groups, are needed. We have not examined the possible harmful effects of antenatal corticosteroids in low-resource settings in this review. It would be particularly relevant to explore this finding in adequately powered prospective trials.
Topics: Adrenal Cortex Hormones; Betamethasone; Dexamethasone; Female; Fetal Organ Maturity; Humans; Hydrocortisone; Infant, Newborn; Lung; Maternal Death; Perinatal Death; Pregnancy; Premature Birth; Prenatal Care; Respiratory Distress Syndrome, Newborn
PubMed: 28321847
DOI: 10.1002/14651858.CD004454.pub3