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American Journal of Obstetrics &... Jul 2022Pelvic inflammatory disease during pregnancy is a rare and an understudied occurrence with potential negative outcomes. (Review)
Review
BACKGROUND
Pelvic inflammatory disease during pregnancy is a rare and an understudied occurrence with potential negative outcomes.
OBJECTIVE
This study aimed to evaluate the outcomes of pregnant women with pelvic inflammatory disease with or without pelvic abscesses.
DATA SOURCES
We performed a systematic review of the literature using Ovid MEDLINE, Scopus, CINAHL, and PubMed (including Cochrane) with no time limitations.
STUDY ELIGIBILITY CRITERIA
Relevant studies on pelvic inflammatory disease during pregnancy were identified and considered eligible if they described at least 1 case of pelvic inflammatory disease after conception, defined as infection in one or more of the following: uterus, fallopian tubes, and ovaries; based on clinical findings, physical examination, and imaging with or without pelvic abscesses present. Only studies on pelvic inflammatory disease with or without tubo-ovarian abscesses during pregnancy that evaluated perinatal outcomes were included. Data on the risk factors, delivery methods, and maternal, fetal, and neonatal outcomes were collected.
METHODS
Reviewers screened all relevant titles using the inclusion/exclusion criteria and selected relevant articles for appraisal. A total of 49 cases with reported pelvic inflammatory disease, pelvic abscesses, or both were included.
RESULTS
After exclusion of articles that did not meet the inclusion criteria, 34 manuscripts describing the occurrence of pelvic inflammatory disease in 49 pregnancies were analyzed, focusing primarily on cases reported after 1971. The mean age of patients was 25±6.3 years, the mean gestational age at diagnosis was 19.0±10.3 weeks, and 67.6% of patients were multiparous. Of all included patients, 27 (62.8%) underwent exploratory laparotomies, 14 (32.6%) underwent unilateral salpingo-oophorectomies, and 11 (25.6%) underwent appendectomies. Of all the deliveries, 13 (50%) pregnancies were full term, 14 (53.8%) were cesarean deliveries, 10 (38.5%) were spontaneous vaginal deliveries, and 2 (7.7%) were cesarean hysterectomies. There were 26 (60.5%) cases of viable births (mean gestational age at delivery, 33.8±5.1 weeks) and 17 (39.5%) cases of nonviable births. Sepsis was a complication in 3 (7.0%) cases and caused 3 neonatal deaths.
CONCLUSION
Although rare, pelvic inflammatory disease can have severe health consequences. Risk factors for pelvic inflammatory disease development include maternal pelvic structural anomalies, a history of sexually transmitted infections, recent pelvic surgery, and in vitro fertilization or oocyte retrieval. Pelvic inflammatory disease can coincide with pregnancy and can occur in the second trimester. Making a prompt diagnosis can help to improve the outcomes; therefore, if a high enough suspicion exists, treatment should not be delayed.
Topics: Abscess; Cesarean Section; Female; Gestational Age; Humans; Parturition; Pelvic Inflammatory Disease; Pregnancy
PubMed: 35405372
DOI: 10.1016/j.ajogmf.2022.100643 -
Prenatal Diagnosis Jun 2017With a high sensitivity and specificity, non-invasive prenatal testing (NIPT) is an incomparable screening test for fetal aneuploidy. However, the method is rather newly... (Review)
Review
With a high sensitivity and specificity, non-invasive prenatal testing (NIPT) is an incomparable screening test for fetal aneuploidy. However, the method is rather newly introduced, and experiences with discordant results are few. We did a systematic review of literature reporting details of false positive and false negative NIPT results. Discordant sex chromosome results were not included. We identified 22 studies reporting case details. In total, 206 discordant cases were included, of which 88% were false positive and 12% false negative. Details on maternal age, gestational age, platform/company, Z-score, fetal fraction, results and explanation were specified. The main reasons for discordant results were confined placental mosaicism, maternal copy number variation, vanished twin, maternal cancer and true fetal mosaicism. A very high percentage of cases (67%) were reported with no obvious biological or technical explanation for the discordant result. The included cases represent only a minor part of the true number of false positive or false negative NIPT cases identified in fetal medicine clinics around the world. To ensure knowledge exchange and transparency of NIPT between laboratories, we suggest a systematic recording of discordant NIPT results, as well as a quality assurance by external quality control and accreditation. © 2017 John Wiley & Sons, Ltd.
Topics: Chromosome Aberrations; False Negative Reactions; False Positive Reactions; Female; Humans; Maternal Serum Screening Tests; Pregnancy
PubMed: 28382695
DOI: 10.1002/pd.5049 -
The Cochrane Database of Systematic... Apr 2017Multiple-micronutrient (MMN) deficiencies often coexist among women of reproductive age in low- to middle-income countries. They are exacerbated in pregnancy due to the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple-micronutrient (MMN) deficiencies often coexist among women of reproductive age in low- to middle-income countries. They are exacerbated in pregnancy due to the increased demands, leading to potentially adverse effects on the mother and developing fetus. Though supplementation with MMNs has been recommended earlier because of the evidence of impact on pregnancy outcomes, a consensus is yet to be reached regarding the replacement of iron and folic acid supplementation with MMNs. Since the last update of this Cochrane review, evidence from a few large trials has recently been made available, the inclusion of which is critical to inform policy.
OBJECTIVES
To evaluate the benefits of oral multiple-micronutrient supplementation during pregnancy on maternal, fetal and infant health outcomes.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (11 March 2015) and reference lists of retrieved articles and key reviews. We also contacted experts in the field for additional and ongoing trials.
SELECTION CRITERIA
All prospective randomised controlled trials evaluating MMN supplementation with iron and folic acid during pregnancy and its effects on the pregnancy outcome were eligible, irrespective of language or the publication status of the trials. We included cluster-randomised trials, but quasi-randomised trials were excluded.
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
Nineteen trials (involving 138,538 women) were identified as eligible for inclusion in this review but only 17 trials (involving 137,791 women) contributed data to the review. Fifteen of these 17 trials were carried out in low and middle-income countries and compared MMN supplements with iron and folic acid versus iron with or without folic acid. Two trials carried out in the UK compared MMN with a placebo. MMN with iron and folic acid versus iron, with or without folic acid (15 trials): MMN resulted in a significant decrease in the number of newborn infants identified as low birthweight (LBW) (average risk ratio (RR) 0.88, 95% confidence interval (CI) 0.85 to 0.91; high-quality evidence) or small-for-gestational age (SGA) (average RR 0.92, 95% CI 0.86 to 0.98; moderate-quality evidence). No significant differences were shown for other maternal and pregnancy outcomes: preterm births (average RR 0.96, 95% CI 0.90 to 1.03; high-quality evidence), stillbirth (average RR 0.97, 95% CI 0.87, 1.09; high-quality evidence), maternal anaemia in the third trimester (average RR 1.03, 95% CI 0.85 to 1.24), miscarriage (average RR 0.91, 95% CI 0.80 to 1.03), maternal mortality (average RR 0.97, 95% CI 0.63 to 1.48), perinatal mortality (average RR 1.01, 95% CI 0.91 to 1.13; high-quality evidence), neonatal mortality (average RR 1.06, 95% CI 0.92 to 1.22; high-quality evidence), or risk of delivery via a caesarean section (average RR 1.04; 95% CI 0.74 to 1.46).A number of prespecified, clinically important outcomes could not be assessed due to insufficient or non-available data. Single trials reported results for: very preterm birth < 34 weeks, macrosomia, side-effects of supplements, nutritional status of children, and congenital anomalies including neural tube defects and neurodevelopmental outcome: Bayley Scales of Infant Development (BSID) scores. None of these trials reported pre-eclampsia, placental abruption, premature rupture of membranes, cost of supplementation, and maternal well-being or satisfaction.When assessed according to GRADE criteria, the quality of evidence for the review's primary outcomes overall was good. Pooled results for primary outcomes were based on multiple trials with large sample sizes and precise estimates. The following outcomes were graded to be as of high quality: preterm birth, LBW, perinatal mortality, stillbirth and neonatal mortality. The outcome of SGA was graded to be of moderate quality, with evidence downgraded by one for funnel plot asymmetry and potential publication bias.We carried out sensitivity analysis excluding trials with high levels of sample attrition (> 20%); results were consistent with the main analysis except for the findings for SGA (average RR 0.91, 95% CI 0.84 to 1.00). We explored heterogeneity through subgroup analyses by maternal height and body mass index (BMI), timing of supplementation and dose of iron. Subgroup differences were observed for maternal BMI for the outcome preterm birth, with significant findings among women with low BMI. Subgroup differences were also observed for maternal BMI and maternal height for the outcome SGA, indicating a significant impact among women with higher maternal BMI and height. The overall analysis of perinatal mortality, although showed a non-significant effect of MMN supplements versus iron with or without folic acid, was found to have substantial statistical heterogeneity. Subgroup differences were observed for timing of supplementation for this outcome, indicating a significantly higher impact with late initiation of supplementation. The findings between subgroups for other primary outcomes were inconclusive. MMN versus placebo (two trials): A single trial in the UK found no clear differences between groups for preterm birth, SGA, LBW or maternal anaemia in the third trimester. A second trial reported the number of women with pre-eclampsia; there was no evidence of a difference between groups. Other outcomes were not reported.
AUTHORS' CONCLUSIONS
Our findings support the effect of MMN supplements with iron and folic acid in improving some birth outcomes. Overall, pregnant women who received MMN supplementation had fewer low birthweight babies and small-for-gestational-age babies. The findings, consistently observed in several systematic evaluations of evidence, provide a basis to guide the replacement of iron and folic acid with MMN supplements containing iron and folic acid for pregnant women in low and middle-income countries where MMN deficiencies are common among women of reproductive age. Efforts could focus on the integration of this intervention in maternal nutrition and antenatal care programs in low and middle-income countries.
Topics: Dietary Supplements; Drug Interactions; Female; Folic Acid; Humans; Iron, Dietary; Micronutrients; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Randomized Controlled Trials as Topic
PubMed: 28407219
DOI: 10.1002/14651858.CD004905.pub5 -
Annals of the New York Academy of... Aug 2019Maternal anemia is a well-recognized global health problem; however, there remain questions on specific hemoglobin (Hb) thresholds that predict health risk or protection... (Meta-Analysis)
Meta-Analysis
Maternal anemia is a well-recognized global health problem; however, there remain questions on specific hemoglobin (Hb) thresholds that predict health risk or protection for mother and child. We conducted a systematic review and meta-analysis to examine the associations of maternal Hb concentrations with a range of maternal and infant health outcomes, accounting for the timing of measurement (preconception, and first, second, and third trimesters), etiology of anemia, and cutoff category. The systematic review included 272 studies and the meta-analysis included 95 studies. Low maternal Hb (<110 g/L) was associated with poor birth outcomes (low birth weight, preterm birth, small-for-gestational-age (SGA), stillbirth, and perinatal and neonatal mortality) and adverse maternal outcomes (postpartum hemorrhage, preeclampsia, and blood transfusion). High maternal Hb (>130 g/L) was associated with increased odds of SGA, stillbirth, preeclampsia, and gestational diabetes. Relationships varied by the timing of measurement and cutoff category (stronger associations with lower cutoffs); limited data were available on anemia etiology. There were insufficient data for other maternal outcomes and long-term child health outcomes. Current data are insufficient for determining if revisions to current Hb cutoffs are required. Pooled high-quality individual-level data analyses, as well as prospective cohort studies, would be valuable to inform the reevaluation of Hb cutoffs.
Topics: Child Health; Female; Hemoglobins; Humans; Infant, Small for Gestational Age; Maternal Health; Obstetric Labor Complications; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth
PubMed: 30994929
DOI: 10.1111/nyas.14093 -
Archives of Iranian Medicine Feb 2020Diagnosis and timely treatment of neonatal jaundice and prevention of dangerous side effects of pathologic neonatal jaundice remain a serious debate. The first step in...
BACKGROUND
Diagnosis and timely treatment of neonatal jaundice and prevention of dangerous side effects of pathologic neonatal jaundice remain a serious debate. The first step in prevention of jaundice is the identification of predisposing factors. The present study aims to systematically review the maternal risk factors of neonatal hyperbilirubinemia.
METHODS
For this study, we searched databases including Science Direct, Cochrane Library, ISI, PubMed and Google Scholar from 1993 to 2017. The keywords searched based on MESH included hyperbilirubinemia, jaundice, infants, mothers and risk factors. The present systematic review was conducted on studies reporting maternal risk factors for neonatal jaundice. The inclusion criteria were: study on neonates; examination of maternal factors or both maternal and neonatal factors. Papers associated with the diagnosis and treatment of neonatal jaundice were excluded from the study, as well as those articles for which only abstracts were available. The limitations of this study include lack of access to all relevant articles, lack of qualified reports in some papers, and the limitation in number of articles related to maternal risk factors, and therefore inability to judge accurately about their effects on neonatal jaundice.
RESULTS
Of 500 searched articles, 17 articles (1 prospective article, 2 retrospective papers, 12 cross-sectional papers and 2 historical cohort articles) were finally investigated. Maternal risk factors included hypertension, diabetes, type of delivery, vaginal bleeding, premature rupture of membranes (PROM), maternal age, lack of initiation of feeding during the first hours of life, inappropriate breastfeeding techniques and presence of maternal breast problems.
CONCLUSION
The most common maternal risk factors for neonatal jaundice were prematurity, blood type incompatibilities, preeclampsia, hypertension, diabetes mellitus, vaginal bleeding, delivery problems (type of delivery, labor injuries, delivery at home, skin ecchymosis, and cephalohematoma), mothers and community cultural beliefs (use of traditional supplements), breast problems, and decrease in breastfeeding.
Topics: Delivery, Obstetric; Female; Humans; Hyperbilirubinemia, Neonatal; Infant, Newborn; Infant, Premature; Male; Pregnancy; Pregnancy Complications; Risk Factors
PubMed: 32061076
DOI: No ID Found -
Obesity Research & Clinical Practice 2021Systematic review and meta-analysis conducted to investigate the effect of stratified pre-pregnancy maternal body mass index on twenty maternal and fetal/neonatal... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Systematic review and meta-analysis conducted to investigate the effect of stratified pre-pregnancy maternal body mass index on twenty maternal and fetal/neonatal adverse outcomes.
METHODS
PubMed, Google Scholar, Medline, Embase, Web of Science databases were searched from inception till July 11, 2020. Cohort studies were included. The pooled odds ratio with 95% confidence interval was reported considering the random effect and the quality effect model. The sub-group analysis and meta-regression were conducted for BMI cut-offs, geographical region, source of BMI, and sample size.
RESULTS
Overall, 86 studies representing 20,328,777 pregnant women were included in this meta-analysis. Our study reveals that overweight and obese mothers are at increased odds of cesarean delivery, elective cesarean delivery, emergency cesarean delivery, gestational diabetes, gestational hypertension, induction of labor, postpartum hemorrhage, pre-eclampsia, pre-term premature rupture of membrane, and the fetuses/neonates of overweight and obese mothers are at increased risk of admission in the newborn intensive care unit, APGAR scores less than 7 at 5 min, large for gestational age, macrosomia, extreme pre-term birth in pregnant mothers compared with standard BMI mothers. However, the underweight mothers showed increased odds for small for gestational age infant and pre-term birth, whereas obese mothers were at higher risk for post-term birth and stillbirths. The subgroup and meta-regression analyses have shown the impact of BMI cut-offs, geographical region, source of BMI, and sample size on several maternal, fetal/neonatal adverse outcomes.
CONCLUSION
The meta-analysis confirmed the association of elevated pre-pregnancy maternal BMI with higher odds of adverse maternal and fetal/neonatal outcomes.
Topics: Body Mass Index; Diabetes, Gestational; Female; Fetal Macrosomia; Humans; Infant, Newborn; Pregnancy; Pregnancy Outcome; Premature Birth
PubMed: 34782256
DOI: 10.1016/j.orcp.2021.10.005 -
The Lancet. Diabetes & Endocrinology Jun 2020Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight.
METHODS
In this systematic review and individual-participant data meta-analysis, we searched MEDLINE (Ovid), Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception to Oct 15, 2019, for prospective cohort studies with data on maternal thyroid function during pregnancy and birthweight, and we issued open invitations to identify study authors to join the Consortium on Thyroid and Pregnancy. We excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birthweight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496.
FINDINGS
We identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother-child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT]) and 929 (2·2%) had isolated hypothyroxinaemia (decreased FT with normal TSH). Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birthweight (mean difference -38 g, -61 to -15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second. Isolated hypothyroxinaemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference -2·91, -4·49 to -0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birthweight (mean difference 45 g, 18 to 73; p=0·0012). Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birthweight (-10 to -2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (p=0·10). Each 1 SD increase in FT concentration was associated with a 21 g lower birthweight (-25 to -17; p<0·0001), with a higher effect estimate for measurement in the third trimester than the first or second.
INTERPRETATION
Maternal subclinical hypothyroidism in pregnancy is associated with a higher risk of SGA and lower birthweight, whereas isolated hypothyroxinaemia is associated with lower risk of SGA and higher birthweight. There was an inverse, dose-response association of maternal TSH and FT (even within the normal range) with birthweight. These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy.
FUNDING
Netherlands Organization for Scientific Research (grant 401.16.020).
Topics: Birth Weight; Female; Gestational Age; Humans; Hypothyroidism; Infant, Low Birth Weight; Infant, Newborn; Pregnancy; Pregnancy Complications; Thyroid Function Tests; Thyroid Gland
PubMed: 32445737
DOI: 10.1016/S2213-8587(20)30061-9 -
Risks associated with obesity in pregnancy, for the mother and baby: a systematic review of reviews.Obesity Reviews : An Official Journal... Aug 2015Maternal obesity is linked with adverse outcomes for mothers and babies. To get an overview of risks related to obesity in pregnant women, a systematic review of reviews... (Review)
Review
Maternal obesity is linked with adverse outcomes for mothers and babies. To get an overview of risks related to obesity in pregnant women, a systematic review of reviews was conducted. For inclusion, reviews had to compare pregnant women of healthy weight with women with obesity, and measure a health outcome for mother and/or baby. Authors conducted full-text screening, quality assurance using the AMSTAR tool and data extraction steps in pairs. Narrative analysis of the 22 reviews included show gestational diabetes, pre-eclampsia, gestational hypertension, depression, instrumental and caesarean birth, and surgical site infection to be more likely to occur in pregnant women with obesity compared with women with a healthy weight. Maternal obesity is also linked to greater risk of preterm birth, large-for-gestational-age babies, foetal defects, congenital anomalies and perinatal death. Furthermore, breastfeeding initiation rates are lower and there is greater risk of early breastfeeding cessation in women with obesity compared with healthy weight women. These adverse outcomes may result in longer duration of hospital stay, with concomitant resource implications. It is crucial to reduce the burden of adverse maternal and foetal/child outcomes caused by maternal obesity. Women with obesity need support to lose weight before they conceive, and to minimize their weight gain in pregnancy.
Topics: Adult; Breast Feeding; Cesarean Section; Depression; Directive Counseling; Female; Health Knowledge, Attitudes, Practice; Humans; Infant, Low Birth Weight; Infant, Newborn; Male; Molecular Sequence Data; Mothers; Obesity; Perinatal Mortality; Pre-Eclampsia; Preconception Care; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Risk Factors; Social Support; Weight Gain; Weight Reduction Programs
PubMed: 26016557
DOI: 10.1111/obr.12288 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2020Maternal vitamin D deficiency has been associated with an increased risk for preeclampsia. Despite this, the current evidence regarding the efficacy of vitamin D... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Maternal vitamin D deficiency has been associated with an increased risk for preeclampsia. Despite this, the current evidence regarding the efficacy of vitamin D supplementation in preventing preeclampsia is controversial. To assess the impact of vitamin D supplementation on the risk of preeclampsia, we performed a systematic review of the literature and a meta-analysis of the available randomized clinical trials (RCTs).
METHODS
The primary outcome was preeclampsia. Subgroup analyses were carried out considering the timing of the supplementation, type of intervention and the study design. Meta-regression analysis, including the amount of vitamin D and maternal age, were planned to explore heterogeneity (PROSPERO database registration number: CRD42019119207).
RESULTS
Data were pooled from 27 RCTs comprising 59 arms, which included overall 4777 participants, of whom 2487 were in the vitamin D-treated arm and 2290 in the control arm. Vitamin D administration in pregnancy was associated with a reduced risk of preeclampsia (odd ratio [OR] 0.37, 95% confidence interval [CI]: 0.26, 0.52; I = 0%). If the vitamin D supplementation was started up to 20 weeks' gestation, the odds was a little lower (OR 0.35, 95% CI: 0.24, 0.50, p < 0.001). The effect was largely independent of the supplementation cessation (until delivery or not), type of intervention (vitamin D alone or in association with calcium), and study design. Increasing dose of vitamin D was associated with reduced incidence of preeclampsia (slope of log OR: -1.1, 95% CI: -1.73, -0.46; p < 0.001).
CONCLUSIONS
Results suggest that vitamin D supplementation may be useful in preventing preeclampsia. These data are especially useful for health-care providers who engage in the management of pregnant women at risk for preeclampsia. Our findings are a call for action to definitively address vitamin D supplementation as a possible intervention strategy in preventing preeclampsia in pregnancy.
Topics: Adolescent; Adult; Avitaminosis; Dietary Supplements; Female; Humans; Incidence; Middle Aged; Pre-Eclampsia; Pregnancy; Protective Factors; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome; Vitamin D; Young Adult
PubMed: 31526611
DOI: 10.1016/j.clnu.2019.08.015 -
Human Reproduction Update Sep 2023A normal chromosomal constitution defined through PGT-A assessing all chromosomes on trophectoderm (TE) biopsies represents the strongest predictor of embryo... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A normal chromosomal constitution defined through PGT-A assessing all chromosomes on trophectoderm (TE) biopsies represents the strongest predictor of embryo implantation. Yet, its positive predictive value is not higher than 50-60%. This gap of knowledge on the causes of euploid blastocysts' reproductive failure is known as 'the black box of implantation'.
OBJECTIVE AND RATIONALE
Several embryonic, maternal, paternal, clinical, and IVF laboratory features were scrutinized for their putative association with reproductive success or implantation failure of euploid blastocysts.
SEARCH METHODS
A systematic bibliographical search was conducted without temporal limits up to August 2021. The keywords were '(blastocyst OR day5 embryo OR day6 embryo OR day7 embryo) AND (euploid OR chromosomally normal OR preimplantation genetic testing) AND (implantation OR implantation failure OR miscarriage OR abortion OR live birth OR biochemical pregnancy OR recurrent implantation failure)'. Overall, 1608 items were identified and screened. We included all prospective or retrospective clinical studies and randomized-controlled-trials (RCTs) that assessed any feature associated with live-birth rates (LBR) and/or miscarriage rates (MR) among non-mosaic euploid blastocyst transfer after TE biopsy and PGT-A. In total, 41 reviews and 372 papers were selected, clustered according to a common focus, and thoroughly reviewed. The PRISMA guideline was followed, the PICO model was adopted, and ROBINS-I and ROB 2.0 scoring were used to assess putative bias. Bias across studies regarding the LBR was also assessed using visual inspection of funnel plots and the trim and fill method. Categorical data were combined with a pooled-OR. The random-effect model was used to conduct the meta-analysis. Between-study heterogeneity was addressed using I2. Whenever not suitable for the meta-analysis, the included studies were simply described for their results. The study protocol was registered at http://www.crd.york.ac.uk/PROSPERO/ (registration number CRD42021275329).
OUTCOMES
We included 372 original papers (335 retrospective studies, 30 prospective studies and 7 RCTs) and 41 reviews. However, most of the studies were retrospective, or characterized by small sample sizes, thus prone to bias, which reduces the quality of the evidence to low or very low. Reduced inner cell mass (7 studies, OR: 0.37, 95% CI: 0.27-0.52, I2 = 53%), or TE quality (9 studies, OR: 0.53, 95% CI: 0.43-0.67, I2 = 70%), overall blastocyst quality worse than Gardner's BB-grade (8 studies, OR: 0.40, 95% CI: 0.24-0.67, I2 = 83%), developmental delay (18 studies, OR: 0.56, 95% CI: 0.49-0.63, I2 = 47%), and (by qualitative analysis) some morphodynamic abnormalities pinpointed through time-lapse microscopy (abnormal cleavage patterns, spontaneous blastocyst collapse, longer time of morula formation I, time of blastulation (tB), and duration of blastulation) were all associated with poorer reproductive outcomes. Slightly lower LBR, even in the context of PGT-A, was reported among women ≥38 years (7 studies, OR: 0.87, 95% CI: 0.75-1.00, I2 = 31%), while obesity was associated with both lower LBR (2 studies, OR: 0.66, 95% CI: 0.55-0.79, I2 = 0%) and higher MR (2 studies, OR: 1.8, 95% CI: 1.08-2.99, I2 = 52%). The experience of previous repeated implantation failures (RIF) was also associated with lower LBR (3 studies, OR: 0.72, 95% CI: 0.55-0.93, I2 = 0%). By qualitative analysis, among hormonal assessments, only abnormal progesterone levels prior to transfer were associated with LBR and MR after PGT-A. Among the clinical protocols used, vitrified-warmed embryo transfer was more effective than fresh transfer (2 studies, OR: 1.56, 95% CI: 1.05-2.33, I2 = 23%) after PGT-A. Lastly, multiple vitrification-warming cycles (2 studies, OR: 0.41, 95% CI: 0.22-0.77, I2 = 50%) or (by qualitative analysis) a high number of cells biopsied may slightly reduce the LBR, while simultaneous zona-pellucida opening and TE biopsy allowed better results than the Day 3 hatching-based protocol (3 studies, OR: 1.41, 95% CI: 1.18-1.69, I2 = 0%).
WIDER IMPLICATIONS
Embryo selection aims at shortening the time-to-pregnancy, while minimizing the reproductive risks. Knowing which features are associated with the reproductive competence of euploid blastocysts is therefore critical to define, implement, and validate safer and more efficient clinical workflows. Future research should be directed towards: (i) systematic investigations of the mechanisms involved in reproductive aging beyond de novo chromosomal abnormalities, and how lifestyle and nutrition may accelerate or exacerbate their consequences; (ii) improved evaluation of the uterine and blastocyst-endometrial dialogue, both of which represent black boxes themselves; (iii) standardization/automation of embryo assessment and IVF protocols; (iv) additional invasive or preferably non-invasive tools for embryo selection. Only by filling these gaps we may finally crack the riddle behind 'the black box of implantation'.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Embryo Implantation; Blastocyst; Embryo Transfer; Genetic Testing; Retrospective Studies; Aneuploidy; Pregnancy Rate; Preimplantation Diagnosis
PubMed: 37192834
DOI: 10.1093/humupd/dmad010