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BMC Pregnancy and Childbirth Dec 2023Back pain during pregnancy is often considered as an unavoidable problem and can reduce the quality of life or disability of pregnant women. The aim of this study is to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Back pain during pregnancy is often considered as an unavoidable problem and can reduce the quality of life or disability of pregnant women. The aim of this study is to determine the global prevalence of back pain in pregnancy based on a systematic review and meta-analysis.
METHODS
In this study, Researchers systematically searched electronic databases PubMed, Scopus, Web of Science, Embase, ScienceDirect, and Google Scholar search engines for studies until September 2023. To analyze data, the random effects model was used, and the heterogeneity of the studies was checked with the I2 index. Data analysis was performed by software (Version 2 Comprehensive Meta-Analysis).
RESULTS
In the review of 28 studies with a sample size of 12,908 people, the I heterogeneity test showed high heterogeneity (I: 98.4). Based on this, the random effects method was used to analyze the results. Therefore, the meta-analysis reported the global prevalence of back pain at 40.5 (95% CI: 33-48.4) during pregnancy. Also, according to the meta-analysis, the global prevalence of back pain in the first trimester of pregnancy is 28.3 (95%CI: 10.5-57.1), in the second trimester is 36.8 (95%CI: 30.4-43.7) and in the third trimester of pregnancy was reported as 47.8 (95% CI: 37.2-58.6).
CONCLUSION
In this meta-analysis, the overall prevalence of back pain in pregnant women was reported to be significant, so it is necessary for health policymakers to pay more attention to complications during pregnancy, in addition to increasing society's awareness of pregnant mothers, with timely diagnosis and treatment of such disorders, it can lead to improvement; and reduction in Complications caused by pregnancy and becoming more pleasant during pregnancy.
Topics: Pregnancy; Female; Humans; Low Back Pain; Prevalence; Quality of Life; Pregnant Women; Back Pain
PubMed: 38042815
DOI: 10.1186/s12884-023-06151-x -
Journal of Obstetrics and Gynaecology :... Dec 2023Previous studies evaluating the relationship between blood manganese (Mn) level and gestational diabetes mellitus (GDM) in pregnant women showed inconsistent results. A... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies evaluating the relationship between blood manganese (Mn) level and gestational diabetes mellitus (GDM) in pregnant women showed inconsistent results. A systematic review and meta-analysis was therefore performed to investigate the above association.
METHODS
Relevant observational studies were obtained by search of electronic databases including Medline, Embase, Cochrane Library and Web of Science from database inception to 10 March 2023. Two authors independently performed database search, literature identification and data extraction. A randomised-effects model was selected to pool the data by incorporating the influence of potential heterogeneity. Subgroup analysis was performed to evaluate the influence of study characteristics on the results of the meta-analysis.
RESULTS
Six datasets from five observational studies, involving 91,249 pregnant women were included in the meta-analysis. Among the participants, 3597 (3.9%) were diagnosed as GDM. Overall, pooled results showed that a high blood level of Mn was associated with a higher risk of GDM (compared between women with highest versus lowest category blood Mn, odds ratio: 1.31, 95% confidence interval: 1.19-1.44, < .001) with no significant heterogeneity ( for Cochrane -test = 0.93, = 0%). Subgroup analyses according to study design, mean maternal age, matrix or methods for measuring blood Mn, and the incidence of GDM also showed consistent results ( for subgroup difference all >.05).
CONCLUSIONS
Results of the meta-analysis suggest that a high blood Mn level may be a risk factor of GDM in pregnant women. Studies are needed to determine the underlying mechanisms, and to investigate if the relationship between blood Mn level and GDM is dose-dependent.
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Manganese; Risk Factors; Maternal Age; Odds Ratio
PubMed: 37921106
DOI: 10.1080/01443615.2023.2266646 -
The Cochrane Database of Systematic... Sep 2023Many factors influence fertility, one being the timing of intercourse. The 'fertile window' describes a stage in the cycle when conception can occur and is approximately... (Review)
Review
BACKGROUND
Many factors influence fertility, one being the timing of intercourse. The 'fertile window' describes a stage in the cycle when conception can occur and is approximately five days before to several hours after ovulation. 'Timed intercourse' is the practice of prospectively identifying ovulation and, thus, the fertile window to increase the likelihood of conception. Methods of predicting ovulation include urinary hormone measurement (luteinising hormone (LH) and oestrogen), fertility awareness-based methods (FABM) (including tracking basal body temperatures, cervical mucus monitoring, calendar charting/tracking apps), and ultrasonography. However, there are potentially negative aspects associated with ovulation prediction, including stress, time consumption, and cost implications of purchasing ovulation kits and app subscriptions. This review considered the evidence from randomised controlled trials (RCTs) evaluating the use of timed intercourse (using ovulation prediction) on pregnancy outcomes.
OBJECTIVES
To evaluate the benefits and risks of ovulation prediction methods for timing intercourse on conception in couples trying to conceive.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group Specialised Register, CENTRAL, MEDLINE, and Embase in January 2023. We also checked the reference lists of relevant studies and searched trial registries for any additional trials.
SELECTION CRITERIA
We included RCTs that compared methods of timed intercourse using ovulation prediction to other forms of ovulation prediction or intercourse without ovulation prediction in couples trying to conceive.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane to select and analyse studies in this review. The primary review outcomes were live birth and adverse events (such as depression and stress). Secondary outcomes were clinical pregnancy, pregnancy (clinical or positive urinary pregnancy test not yet confirmed by ultrasound), time to pregnancy, and quality of life. We assessed the overall quality of the evidence for the main comparisons using GRADE methods.
MAIN RESULTS
This review update included seven RCTs involving 2464 women or couples. Four of the five studies from the previous review were included in this update, and three new studies were added. We assessed the quality of the evidence as moderate to very low, the main limitations being imprecision, indirectness, and risk of bias. Urinary ovulation tests versus intercourse without ovulation prediction Compared to intercourse without ovulation prediction, urinary ovulation detection probably increases the chance of live birth in couples trying to conceive (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.02 to 1.81, 1 RCT, n = 844, moderate-quality evidence). This suggests that if the chance of a live birth without urine ovulation prediction is 16%, the chance of a live birth with urine ovulation prediction is 16% to 28%. However, we are uncertain whether timed intercourse using urinary ovulation detection resulted in a difference in stress (mean difference (MD) 1.98, 95% CI -0.87 to 4.83, I² = 0%, P = 0.17, 1 RCT, n = 77, very low-quality evidence) or clinical pregnancy (RR 1.09, 95% CI 0.51 to 2.31, I² = 0%, 1 RCT, n = 148, low-quality evidence). Similar to the live birth result, timed intercourse using urinary ovulation detection probably increases the chances of clinical pregnancy or positive urine pregnancy test (RR 1.28, 95% CI 1.09 to 1.50, I² = 0, 4 RCTs, n = 2202, moderate-quality evidence). This suggests that if the chance of a clinical pregnancy or positive urine pregnancy test without ovulation prediction is assumed to be 18%, the chance following timed intercourse with urinary ovulation detection would be 20% to 28%. Evidence was insufficient to determine the effect of urine ovulation tests on time to pregnancy or quality of life. Fertility awareness-based methods (FABM) versus intercourse without ovulation prediction Due to insufficient evidence, we are uncertain whether timed intercourse using FABM resulted in a difference in live birth rate compared to intercourse without ovulation prediction (RR 0.95, 95% CI 0.76 to 1.20, I² = 0%, 2 RCTs, n = 157, low-quality evidence). We are also uncertain whether FABM affects stress (MD -1.10, 95% CI -3.88 to 1.68, 1 RCT, n = 183, very low-quality evidence). Similarly, we are uncertain of the effect of timed intercourse using FABM on anxiety (MD 0.5, 95% CI -0.52 to 1.52, P = 0.33, 1 RCT, n = 183, very low-quality evidence); depression (MD 0.4, 95% CI -0.28 to 1.08, P = 0.25, 1 RCT, n = 183, very low-quality evidence); or erectile dysfunction (MD 1.2, 95% CI -0.38 to 2.78, P = 0.14, 1 RCT, n = 183, very low-quality evidence). Evidence was insufficient to detect a benefit of timed intercourse using FABM on clinical pregnancy (RR 1.13, 95% CI 0.31 to 4.07, 1 RCT, n = 17, very low-quality evidence) or clinical or positive pregnancy test rates (RR 1.08, 95% CI 0.89 to 1.30, 3 RCTs, n = 262, very low-quality evidence). Finally, we are uncertain whether timed intercourse using FABM affects the time to pregnancy (hazard ratio 0.86, 95% CI 0.53 to 1.38, 1 RCT, n = 140, low-quality evidence) or quality of life. No studies assessed the use of timed intercourse with pelvic ultrasonography.
AUTHORS' CONCLUSIONS
The new evidence presented in this review update shows that timed intercourse using urine ovulation tests probably improves live birth and pregnancy rates (clinical or positive urine pregnancy tests but not yet confirmed by ultrasound) in women under 40, trying to conceive for less than 12 months, compared to intercourse without ovulation prediction. However, there are insufficient data to determine the effects of urine ovulation tests on adverse events, clinical pregnancy, time to pregnancy, and quality of life. Similarly, due to limited data, we are uncertain of the effect of FABM on pregnancy outcomes, adverse effects, and quality of life. Further research is therefore required to fully understand the safety and effectiveness of timed intercourse for couples trying to conceive. This research should include studies reporting clinically relevant outcomes such as live birth and adverse effects in fertile and infertile couples and utilise various methods to determine ovulation. Only with a comprehensive understanding of the risks and benefits of timed intercourse can recommendations be made for all couples trying to conceive.
Topics: Male; Female; Humans; Pregnancy; Odds Ratio; Pregnancy, Multiple; Uncertainty; Anxiety; Anxiety Disorders; Drug-Related Side Effects and Adverse Reactions
PubMed: 37709293
DOI: 10.1002/14651858.CD011345.pub3 -
Journal of the European Academy of... Mar 2024The main purpose of this review was to examine the evidence of the relationship between active smoking or passive smoking during pregnancy and atopic dermatitis in... (Review)
Review
The main purpose of this review was to examine the evidence of the relationship between active smoking or passive smoking during pregnancy and atopic dermatitis in offspring. The protocol was written following the PRISMA Checklist and was registered in the PROSPERO database (registration number CRD42022381136). We implemented a comprehensive search in PubMed, Embase and Web of Science databases to identify all potentially related articles from inception through 1 December 2022. We assessed cohort studies and case-control studies using the Newcastle-Ottawa Scale (NOS), and the Joanna Briggs Institute (JBI) critical appraisal tool to assess the quality of cross-sectional studies. Heterogeneity was investigated by using Cochrane Q tests and I statistics. In addition, according to the research design, population source and population size, the reasons for the heterogeneity were analysed. A total of 15 observational studies were included in this analysis. Our meta-analysis suggests that atopic dermatitis in offspring is not associated with active smoking during pregnancy (pooled OR, 0.96 [95% CI 0.86-1.07]); however, it is related to passive smoking (OR, 1.52 [95% CI 1.36-1.70]). Passive smoking during pregnancy is associated with an increased risk of eczema development in offspring. More research is needed to explore the risk of active smoking and eczema development in offspring, especially the association between measurements of pregnancy cotinine levels in maternal body fluids and AD in offspring.
PubMed: 38483217
DOI: 10.1111/jdv.19958 -
Journal of Reproduction & Infertility 2023Cell-free fetal DNA (cffDNA) is a novel screening method for fetal aneuploidy that facilitated non-invasive prenatal testing (NIPT) through analysis of cffDNA in... (Review)
Review
BACKGROUND
Cell-free fetal DNA (cffDNA) is a novel screening method for fetal aneuploidy that facilitated non-invasive prenatal testing (NIPT) through analysis of cffDNA in maternal plasma. However, despite increased sensitivity, it has a number of limitations that may complicate of its results interpretation. Therefore, elucidating factors affecting fetal fraction, as a critical limitation, guides its clinical application.
METHODS
In this report, systematic search was carried out through PubMed, Web of Science, and Scopus databases until February 11, 2022 by using keywords consist of "noninvasive prenatal screening", "NIPT", "noninvasive prenatal", "cell free DNA" and "fetal fraction". The articles were screened for eligibility criteria before data extraction.
RESULTS
A total of 39 eligible studies, most published between 2010 and 2020, were included. Based on the results of studies, a negative correlation between maternal age and BMI/body weight with fetal fraction was found. Furthermore, LDL, cholesterol, triglyceride level, metformin, heparin and enoxaparin therapy, hemoglobin-related hemoglobinopathies, and physical activity showed to have negative associations. Interestingly, it seems the ethnicity of patients from South and East Asia has a correlation with fetal fraction compared to Caucasians. Positive correlation was observed between gestational age, free β-hCG, PAPP-A, living in high altitude, and twin pregnancy.
CONCLUSION
Considering each factor, there was significant inconsistency and controversy regarding their impact on outcomes. Indeed, multiple factors can influence the accuracy of NIPS results, and it is worth noting that the impact of these factors may vary depending on the individual's ethnic background. Therefore, it is important to recognize that NIPS remains a screening test, and comprehensive pre- and post-NIPS counseling should be conducted as part of standard clinical practice.
PubMed: 38164433
DOI: 10.18502/jri.v24i4.14149 -
Contraception and Reproductive Medicine Nov 2023Unintended pregnancy is a leading cause of maternal mortality associated with abortion, inadequate contraceptive use, contraceptive failure, and contraceptive... (Review)
Review
INTRODUCTION
Unintended pregnancy is a leading cause of maternal mortality associated with abortion, inadequate contraceptive use, contraceptive failure, and contraceptive discontinuation in low- and middle-income countries. Most unintended pregnancies occur in regions with limited availability of maternal health services, resulting in a significant number of maternal deaths. Therefore, this review aimed to assess the overall prevalence of unintended pregnancy among women using contraceptives in low- and middle-income countries.
METHOD
PubMed, Science Direct, Google Scholar, Scopus, and the Ethiopian University Online Library were searched. Data were extracted using Microsoft Excel and analyzed using STATA statistical software (version 14). Publication bias was checked using forest plot, Begg rank test, and Egger regression test. To check for heterogeneity, I was calculated and an overall estimation analysis was performed. Subgroup analysis was conducted by study setting, study design, and publication. The Joanna Briggs Institute quality assessment tool was used to assess the quality of each study. We performed a one-time sensitivity analysis.
RESULTS
Of the 1304 articles retrieved, 23 studies (involving 40,338 subjects) met the eligibility criteria and were included in this study. The pooled prevalence of unintended pregnancy among women using contraceptives in low- and middle-income countries was 44.68% (95% CI: 35.16-54.20; I2 = 99.7%, P < 0.001). Based on subgroup analysis, the pooled prevalence of unintended events was 43.58% (CI: 32.99, 54.173) and 49.93% (CI: 28.298, 71.555) for cross-sectional and cohort studies, respectively. Based on the study design, it was 34.47% (CI: 27.012, 41.933) for community studies and 55.85% (CI: 33.364, 78.339) for institutional studies.
CONCLUSION
The overall prevalence of unintended pregnancy was high among women using contraceptives in low- and middle-income countries. Therefore, it is better to pay attention to prevention strategies for unintended pregnancy, such as information and education accessibility and contraceptive utilization.
PubMed: 37993927
DOI: 10.1186/s40834-023-00255-7 -
BMC Pregnancy and Childbirth Oct 2023Skin-to-skin contact between mother and infant after birth is recommended to promote breastfeeding and maternal-infant bonding. However, its impact on the incidence of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Skin-to-skin contact between mother and infant after birth is recommended to promote breastfeeding and maternal-infant bonding. However, its impact on the incidence of neonatal hypoglycaemia is unknown. We conducted a systematic review and meta-analysis to assess this.
METHODS
Published randomised control trials (RCTs), quasi-RCTs, non-randomised studies of interventions, cohort, or case-control studies with an intervention of skin-to-skin care compared to other treatment were included without language or date restrictions. The primary outcome was neonatal hypoglycaemia (study-defined). We searched 4 databases and 4 trial registries from inception to May 12, 2023. Quality of studies was assessed using Cochrane Risk of Bias 1 or Effective Public Health Practice Project Quality Assessment tools. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results were synthesised using RevMan 5.4.1 or STATA and analysed using random-effects meta-analyses where possible, otherwise with direction of findings tables. This review was registered prospectively on PROSPERO (CRD42022328322).
RESULTS
This review included 84,900 participants in 108 studies, comprising 65 RCTs, 16 quasi-RCTs, seven non-randomised studies of intervention, eight prospective cohort studies, nine retrospective cohort studies and three case-control studies. Evidence suggests skin-to-skin contact may result in a large reduction in the incidence of neonatal hypoglycaemia (7 RCTs/quasi-RCTs, 922 infants, RR 0.29 (0.13, 0.66), p < 0.0001, I = 47%). Skin-to-skin contact may reduce the incidence of admission to special care or neonatal intensive care nurseries for hypoglycaemia (1 observational study, 816 infants, OR 0.50 (0.25-1.00), p = 0.050), but the evidence is very uncertain. Skin-to-skin contact may reduce duration of initial hospital stay after birth (31 RCTs, 3437 infants, MD -2.37 (-3.66, -1.08) days, p = 0.0003, I = 90%, p for Egger's test = 0.02), and increase exclusive breastmilk feeding from birth to discharge (1 observational study, 1250 infants, RR 4.30 (3.19, 5.81), p < 0.0001), but the evidence is very uncertain.
CONCLUSION
Skin-to-skin contact may lead to a large reduction in the incidence of neonatal hypoglycaemia. This, along with other established benefits, supports the practice of skin-to-skin contact for all infants and especially those at risk of hypoglycaemia.
Topics: Infant, Newborn; Infant; Female; Humans; Breast Feeding; Mothers; Fetal Diseases; Hypoglycemia; Case-Control Studies; Observational Studies as Topic
PubMed: 37865757
DOI: 10.1186/s12884-023-06057-8 -
Obstetrics and Gynecology Nov 2023To estimate the effect of diabetes group prenatal care on rates of preterm birth and large for gestational age (LGA) among patients with diabetes in pregnancy compared...
OBJECTIVE
To estimate the effect of diabetes group prenatal care on rates of preterm birth and large for gestational age (LGA) among patients with diabetes in pregnancy compared with individual diabetes prenatal care.
DATA SOURCES
We searched Ovid Medline (1946-), Embase.com (1947-), Scopus (1823-), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov.
METHODS OF STUDY SELECTION
We searched electronic databases for randomized controlled trials (RCTs) and observational studies comparing diabetes group prenatal care with individual care among patients with type 2 diabetes mellitus or gestational diabetes mellitus (GDM). The primary outcomes were preterm birth before 37 weeks of gestation and LGA (birth weight at or above the 90th percentile). Secondary outcomes were small for gestational age, cesarean delivery, neonatal hypoglycemia, neonatal intensive care unit admission, breastfeeding at hospital discharge, long-acting reversible contraception (LARC) uptake, and 6-week postpartum visit attendance. Secondary outcomes, limited to the subgroup of patients with GDM, included rates of GDM requiring diabetes medication (A2GDM) and completion of postpartum oral glucose tolerance testing (OGTT). Heterogeneity was assessed with the Cochran Q test and I2 statistic. Random-effects models were used to calculate pooled relative risks (RRs) and weighted mean differences.
TABULATION, INTEGRATION, AND RESULTS
Eight studies met study criteria and were included in the final analysis: three RCTs and five observational studies. A total of 1,701 patients were included in the pooled studies: 770 (45.3%) in diabetes group prenatal care and 931 (54.7%) in individual care. Patients in diabetes group prenatal care had similar rates of preterm birth compared with patients in individual care (seven studies: pooled rates 9.5% diabetes group prenatal care vs 11.5% individual care, pooled RR 0.77, 95% CI, 0.59-1.01), which held for RCTs and observational studies. There was no difference between diabetes group prenatal care and individual care in rates of LGA overall (four studies: pooled rate 16.7% diabetes group prenatal care vs 20.2% individual care, pooled RR 0.93, 95% CI, 0.59-1.45) or by study type. Rates of other secondary outcomes were similar between diabetes group prenatal care and individual care, except patients in diabetes group prenatal care were more likely to receive postpartum LARC (three studies: pooled rates 46.1% diabetes group prenatal care vs 34.1% individual care, pooled RR 1.44, 95% CI, 1.09-1.91). When analysis was limited to patients with GDM, there were no differences in rates of A2GDM or postpartum visit attendance, but patients in diabetes group prenatal care were significantly more likely to complete postpartum OGTT (five studies: pooled rate 74.0% diabetes group prenatal care vs 49.4% individual care, pooled RR 1.58, 95% CI, 1.19-2.09).
CONCLUSION
Patients with type 2 diabetes and GDM who participate in diabetes group prenatal care have similar rates of preterm birth, LGA, and other pregnancy outcomes compared with those who participate in individual care; however, they are significantly more likely to receive postpartum LARC, and those with GDM are more likely to return for postpartum OGTT.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42021279233.
PubMed: 37944148
DOI: 10.1097/AOG.0000000000005442 -
Gynecologic and Obstetric Investigation Mar 2024Vitamin D deficiency increases the risk of adverse pregnancy outcomes. The high prevalence of vitamin D deficiency worldwide requires the analysis of scientific...
Vitamin D deficiency increases the risk of adverse pregnancy outcomes. The high prevalence of vitamin D deficiency worldwide requires the analysis of scientific publications to make recommendations for the prevention, management and treatment of vitamin D deficiency in pregnant women. The purpose of the research was to explore the relationship between pathology and pregnancy outcomes with serum 25-hydroxycholecalciferol levels and vitamin D supplementation. A literature search was performed for systematic literature reviews with meta-analyses published between January 2018 and February 2023. 42 publications were selected for further analysis. 24 meta-analyses evaluated associations between serum 25-hydroxycholecalciferol levels on the one hand and the course and outcome of pregnancy on the other. 18 meta-analyses focused on the preventive effect of vitamin D preparations on the development of obstetric and paediatric pathology. Vitamin D deficiency was identified to increase the probability of spontaneous abortion (OR=1.6 (1.11; 2.3), preterm labour (OR=1.33 (1.15; 1.54)), especially in multiple pregnancies (OR=2.59 (1.35; 4.95)), pre-eclampsia (OR 1.58 (1.39-1.79)), anaemia of pregnancy (OR=1.61 (1.41; 1.83), postpartum depression (OR=3.67 (1.72; 7.85), autism spectrum disorders in early childhood (OR=1.54 (1.12; 2.1). High vitamin D levels reduce the risk of gestational diabetes (RR=0.87 (0.79; 0.97)), and low birth weight (RR=0.65 (0.48; 0.86)). The target level of 25-hydroxyvitamin D during pregnancy is a serum concentration of more than 30 mg/ml. Vitamin D supplementation during pregnancy at a dose of 2000 IU or higher is preventive for pre-eclampsia, insulin resistance, and the development of bronchial asthma in early childhood. Vitamin D screening is indicated for all pregnant women. Dosages of vitamin D preparations should be determined individually, considering laboratory tests and risk factors.
PubMed: 38461819
DOI: 10.1159/000538085 -
Human Reproduction (Oxford, England) Dec 2023How common is bleeding in early pregnancy after Hormone Replacement Therapy (HRT) Frozen Embryo Transfer (FET) and does bleeding affect the reproductive outcome? (Meta-Analysis)
Meta-Analysis
Early pregnancy bleeding after assisted reproductive technology: a systematic review and secondary data analysis from 320 patients undergoing hormone replacement therapy frozen embryo transfer.
STUDY QUESTION
How common is bleeding in early pregnancy after Hormone Replacement Therapy (HRT) Frozen Embryo Transfer (FET) and does bleeding affect the reproductive outcome?
SUMMARY ANSWER
A total of 47% of HRT-FET patients experience bleeding before the eighth week of gestation, however, bleeding does not affect the reproductive outcome.
WHAT IS KNOWN ALREADY
Bleeding occurs in 20% of spontaneously conceived pregnancies, although most will proceed to term. However, our knowledge regarding bleeding in early pregnancy after HRT-FET and the reproductive outcome is sparse.
STUDY DESIGN, SIZE, DURATION
We performed a systematic review of the existing literature on early pregnancy bleeding after assisted reproductive technology (ART) to evaluate the bleeding prevalence and resulting reproductive outcome in this population. A random-effects proportional meta-analysis was conducted. Subsequently, we performed a prospective cohort study including 320 pregnant patients undergoing HRT-FET and a secondary analysis of the cohort study was performed to evaluate bleeding prevalence and reproductive outcome. The trial was conducted from January 2020 to November 2022 in a public fertility clinic.
PARTICIPANTS/MATERIALS, SETTING, METHODS
A systematic literature search was performed, using MESH terms and included studies with data from ART patients and with early pregnancy bleeding as a separate outcome. The cohort study included patients with autologous vitrified blastocyst transfer treated in an HRT-FET protocol. In the event of a positive HCG-test, an early pregnancy scan was performed around 8 weeks of gestation. During this visit, patients answered a questionnaire regarding bleeding or spotting and its duration after the positive pregnancy test. The information was verified through medical files, and these were used to obtain information on reproductive outcomes.
MAIN RESULTS AND THE ROLE OF CHANCE
The review revealed a total of 12 studies of interest. The studies reported a prevalence of early pregnancy bleeding ranging from 2.1% to 36.2%. The random effects proportional meta-analysis resulted in a pooled effect estimate of the prevalence of early pregnancy bleeding in the ART population of 18.1% (95% CI (10.5; 27.1)). Four of the included studies included data on miscarriage rate following an episode of bleeding. All four studies showed a significantly increased risk of miscarriage in patients with early pregnancy bleeding as compared to patients with no history of bleeding. No studies investigated bleeding after HRT-FET specifically. In our HRT-FET cohort study, we found that a total of 47% (149/320) of patients with a positive pregnancy test experienced bleeding before 8 weeks of gestation. Generally, the bleeding was described as spotting with a median of 2 days (range 0.5-16 days). Out of 149 patients with one or several bleeding episodes, a total of 106 patients (71%) had an ongoing pregnancy at 12 weeks of gestation. In comparison, 171 patients reported no bleeding episodes and a total of 115 (67%) of these patients had an ongoing pregnancy at 12 weeks of gestation. This difference was not significant (P = 0.45). Furthermore there was no difference in the live birth rate between the two groups (P = 0.29).
LIMITATIONS, REASONS FOR CAUTION
Most studies included in the review were older and not all studies specified the type of ART. Moreover, the studies were of moderate methodological quality. The patients in the cohort study were treated in a personalized HRT-FET protocol using a rectal supplementary rescue regimen if serum progesterone levels were <35 nmol/l at embryo transfer. The results may not be applicable to other FET protocols, and the present data were based on self-reported symptoms. The systematic review revealed an increased risk of miscarriage following an episode of early pregnancy bleeding. However our cohort study found no such association. This discrepancy can partly be due to the fact, that the four studies in the review only included episodes of heavy bleeding. Also, none of the four studies included data on HRT-FET cycles making them unfit for direct comparison.
WIDER IMPLICATIONS OF THE FINDINGS
Episodes of early bleeding during pregnancy are associated with distress for the pregnant woman, especially in a cohort of infertile patients. Our cohort study showed that at least minor bleeding seems to be a common adverse event of early pregnancy after HRT-FET. From the systematic review, it seems that this prevalence is higher than what has previously been described in relation to other types of ART. However, minor bleeding during early pregnancy after HRT-FET does not seem to affect the reproductive outcome. Knowledge regarding the frequent occurrence of bleeding during early pregnancy after HRT-FET and the fact that this should not be used as a prognostic parameter will help the clinician in counselling patients.
STUDY FUNDING/COMPETING INTEREST(S)
Gedeon Richter Nordic supported this investigator-initiated study with an unrestricted grant as well as study medication (Cyclogest). B.A. has received an unrestricted grant from Gedeon Richter Nordic and Merck and honoraria for lectures from Gedeon Richter, Merck, IBSA, and Marckyrl Pharma. P.H. received honoraria for lectures from Merck, Gedeon Richter, Institut Biochimique SA (IBSA), and Besins as well as unrestricted research grants from Merck, Gedeon Richter, and Institut Biochimique SA (IBSA). The other authors have no conflict of interest to declare.
TRIAL REGISTRATION NUMBER
EudraCT no.: 2019-001539-29.
Topics: Female; Pregnancy; Humans; Pregnancy Rate; Cohort Studies; Abortion, Spontaneous; Prospective Studies; Secondary Data Analysis; Treatment Outcome; Embryo Transfer; Hormone Replacement Therapy
PubMed: 37897214
DOI: 10.1093/humrep/dead218