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Human Reproduction Open 2024Is exposure to dydrogesterone a risk factor for congenital anomalies when given in the first trimester for recurrent/threatened pregnancy loss or as luteal support in... (Review)
Review
STUDY QUESTION
Is exposure to dydrogesterone a risk factor for congenital anomalies when given in the first trimester for recurrent/threatened pregnancy loss or as luteal support in assisted reproductive technology (ART)?
SUMMARY ANSWER
Dydrogesterone, when given in the first trimester for recurrent/threatened pregnancy loss or as luteal support in ART, is not a relevant additional risk factor for congenital anomalies.
WHAT IS KNOWN ALREADY
Despite large clinical trials and meta-analyses that show no association between dydrogesterone and congenital anomalies, some recently retracted publications have postulated an association with teratogenicity. Dydrogesterone is also often rated as less safe than bioidentical progestins.
STUDY DESIGN SIZE DURATION
A systematic review was conducted according to a pre-specified protocol with searches on Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinicaltrials.gov. The search was limited to human studies, with no restrictions on language, geographical region, or date. The search algorithm used a PICO (Population, Intervention, Comparison, Outcome)-style approach combining both simple search terms and medical subject heading terms. As congenital anomalies are mostly reported as secondary outcomes, the search term 'safety' was added.
PARTICIPANTS/MATERIALS SETTING METHODS
Interventional study and observational study (OS) designs were eligible for inclusion. Inclusion criteria were: women >17 years old treated for threatened miscarriage, recurrent pregnancy loss, and/or ART; the use of dydrogesterone in the first trimester compared with placebo, no treatment or other interventions; and reporting of congenital anomalies in newborns or infants ≤12 months old (primary outcome). Two authors (A.K., M.R.N.) independently extracted the following data: general study information, study population details, intervention and comparator(s), and frequencies of congenital anomalies (classification, time of determination, and type). Risk of bias focused on the reporting of congenital malformations and was assessed using the Cochrane Risk of Bias Tool Version 2 or the ROBINS-I tool. The GRADEproGDT platform was used to generate the GRADE summary of findings table.
MAIN RESULTS AND THE ROLE OF CHANCE
Of the 897 records retrieved during the literature search, 47 were assessed for eligibility. Nine studies were included in the final analysis: six randomized controlled trials (RCTs) and three OSs. Among the RCTs, three had a low risk and three a high risk of bias. Two of the OSs were considered to have a serious risk of bias and one with critical risk of bias and was excluded for the evidence syntheses. The eight remaining studies included a total of 5070 participants and 2680 live births from 16 countries. In the meta-analysis of RCTs only, the overall risk ratio (RR) was 0.92 [95% CI 0.55; 1.55] with low certainty. When the two OSs were included, the overall RR was 1.11 [95% CI 0.73; 1.68] with low certainty.
LIMITATIONS REASONS FOR CAUTION
The studies included in the analysis do not report congenital anomalies as the primary outcome; reporting of congenital anomalies was often not standardized.
WIDER IMPLICATIONS OF THE FINDINGS
This systematic literature review and meta-analysis provide clear reassurance to both clinicians and patients that dydrogesterone is not associated with congenital anomalies above the rate that might be expected due to environmental and genetic factors. The results of this work represent the highest current level of evidence for the question of congenital anomalies, which removes the existing uncertainty caused by poor quality and retracted studies.
STUDY FUNDING/COMPETING INTERESTS
Editorial support was provided by Highfield Communication Consultancy, Oxford, UK, sponsored by Abbott Products Operations AG, Allschwil, Switzerland. A.K., J.A.G.-V., L.P.S., J.N.v.d.A., and J.F.S. received honoraria from Abbott for preparation and participation in an advisory board. J.A.G.-V. received grants and lecture fees from Merck, Organon, Ferring, Gedeon Richter, and Theramex. M.R.N. has no conflicts of interest. J.N.v.d.A. and J.A.G.-V. have no other conflicts of interest. A.K. received payment from Abbott for a talk at the IVF Worldwide congress on 22 September 2023. J.F.S. has received grants from the National Institutes of Health, royalties/licences from Elsevier and Prescient Medicine (SOLVD Health), consulting fees from Burroughs Wellcome Fund (BWF) and Bayer, honoraria from Magee Women's Research Institute, Wisconsin National Primate Research Centre, University of Kansas and Oakridge National Research Laboratory, Agile, Daiichi Sankyo/American Regent, and Bayer, and travel support to attend meetings for the International Academy of Human Reproduction (IAHR). J.F.S. has patents related to diagnosis and treatment of PCOS and prediction of preterm birth. J.F.S. participates on advisory boards for SOLVD Health, Wisconsin National Primate Research Centre, and FHI360, was the past President board member of the Society for Reproductive Investigation, has a leadership role for the following organizations: Scientific Advisory Board, SOLVD Health, EAB Chair for contraceptive technology initiative, FHI360, EAB member, Wisconsin National Primate Research Centre, Advisory Board for MWRI Summit, Chair of BWF NextGen Pregnancy Research Panel, Medical Executive Committee at the Howard, and Georgeanna Jones Foundation, and is Vice President, IAHR. L.P.S. has received consulting fees from Shield Pharmaceuticals, Scynexis, Organon, Natera, Celula China, AiVF, Agile, Daiichi Sankyo, American Regent, and Medicem, honoraria from Agile, Daiichi Sankyo/American Regent, and Bayer, and travel support from BD Diagnostics. L.P.S. participates on the data safety monitoring board for Astellas and is a Chair of DSMB for fezolinetant. Abbott played no role in the funding of the study or in study design, data collection, data analysis, data interpretation, or writing of the report.
TRIAL REGISTRATION NUMBER
PROSPERO 2022 CRD42022356977.
PubMed: 38344249
DOI: 10.1093/hropen/hoae004 -
PLoS Medicine Feb 2024Evidence suggests common pathways between pregnancy losses and subsequent long-term maternal morbidity, rendering pregnancy complications an early chronic disease... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence suggests common pathways between pregnancy losses and subsequent long-term maternal morbidity, rendering pregnancy complications an early chronic disease marker. There is a plethora of studies exploring associations between miscarriage and stillbirth with long-term adverse maternal health; however, these data are inconclusive.
METHODS AND FINDINGS
We systematically searched MEDLINE, EMBASE, AMED, BNI, CINAHL, and the Cochrane Library with relevant keywords and MeSH terms from inception to June 2023 (no language restrictions). We included studies exploring associations between stillbirth or miscarriage and incidence of cardiovascular, malignancy, mental health, other morbidities, and all-cause mortality in women without previous pregnancy loss. Studies reporting short-term morbidity (within a year of loss), case reports, letters, and animal studies were excluded. Study selection and data extraction were performed by 2 independent reviewers. Risk of bias was assessed using the Newcastle Ottawa Scale (NOS) and publication bias with funnel plots. Subgroup analysis explored the effect of recurrent losses on adverse outcomes. Statistical analysis was performed using an inverse variance random effects model and results are reported as risk ratios (RRs) with 95% confidence intervals (CIs) and prediction intervals (PIs) by combining the most adjusted RR, odds ratios (ORs) and hazard ratios (HRs) under the rare outcome assumption. We included 56 observational studies, including 45 in meta-analysis. There were 1,119,815 women who experienced pregnancy loss of whom 951,258 had a miscarriage and 168,557 stillbirth, compared with 11,965,574 women without previous loss. Women with a history of stillbirth had a greater risk of ischaemic heart disease (IHD) RR 1.56, 95% CI [1.30, 1.88]; p < 0.001, 95% PI [0.49 to 5.15]), cerebrovascular (RR 1.71, 95% CI [1.44, 2.03], p < 0.001, 95% PI [1.92, 2.42]), and any circulatory/cardiovascular disease (RR 1.86, 95% CI [1.01, 3.45], p = 0.05, 95% PI [0.74, 4.10]) compared with women without pregnancy loss. There was no evidence of increased risk of cardiovascular disease (IHD: RR 1.11, 95% CI [0.98, 1.27], 95% PI [0.46, 2.76] or cerebrovascular: RR 1.01, 95% CI [0.85, 1.21]) in women experiencing a miscarriage. Only women with a previous stillbirth were more likely to develop type 2 diabetes mellitus (T2DM) (RR: 1.16, 95% CI [1.07 to 2.26]; p < 0.001, 95% PI [1.05, 1.35]). Women with a stillbirth history had an increased risk of developing renal morbidities (RR 1.97, 95% CI [1.51, 2.57], p < 0.001, 95% [1.06, 4.72]) compared with controls. Women with a history of stillbirth had lower risk of breast cancer (RR: 0.80, 95% CI [0.67, 0.96], p-0.02, 95% PI [0.72, 0.93]). There was no evidence of altered risk of other malignancies in women experiencing pregnancy loss compared to controls. There was no evidence of long-term mental illness risk in women with previous pregnancy losses (stillbirth: RR 1.90, 95% CI [0.93, 3.88], 95% PI [0.34, 9.51], miscarriage: RR 1.78, 95% CI [0.88, 3.63], 95% PI [1.13, 4.16]). The main limitations include the potential for confounding due to use of aggregated data with variable degrees of adjustment.
CONCLUSIONS
Our results suggest that women with a history of stillbirth have a greater risk of future cardiovascular disease, T2DM, and renal morbidities. Women experiencing miscarriages, single or multiple, do not seem to have an altered risk.
Topics: Pregnancy; Female; Humans; Pregnancy Outcome; Stillbirth; Abortion, Spontaneous; Diabetes Mellitus, Type 2; Cardiovascular Diseases
PubMed: 38335157
DOI: 10.1371/journal.pmed.1004342 -
Iranian Journal of Nursing and... 2024Bacterial infections are among the most serious infections worldwide. They can cause miscarriage, premature birth, stillbirth, and ectopic pregnancy in pregnant women.... (Review)
Review
BACKGROUND
Bacterial infections are among the most serious infections worldwide. They can cause miscarriage, premature birth, stillbirth, and ectopic pregnancy in pregnant women. The aim of this study was to investigate the relationship between bacterial infections and pregnancy outcomes through a systematic review and meta-analysis.
MATERIALS AND METHODS
PubMed, Scopus, Web of Science, and Embase databases were searched from January 2000 to December 2018 using appropriate keywords to identify related articles. The final related studies were selected and evaluated using the Newcastle-Ottawa Scale (NOS).
RESULTS
Results of this meta-analysis based on combining case-control studies showed that the presence of bacterial infections could lead increase in the odds of all pregnancy outcomes like premature infant birth (odd ratio [OR]: 1.50; 95% Confidence Interval [CI], 1.39-1.61), preterm delivery (OR: 1.54; 95% CI, 1.39-1.70), abortion (OR: 1.16; 95% CI, 1.04-1.29), stillbirth (OR, 1.29; 95% CI, 1.12-1.49), and ectopic pregnancy (OR: 1.12; 95% CI, 1.05--1.19). The results showed that the Risk Ratio (RR) of preterm delivery in pregnant women with vaginal infections was 1.57 (95% CI, 1.46-1.67), whereas the RR of abortion was 2.02 (95% CI, 1.72-2.38).
CONCLUSIONS
Based on the results of this meta-analysis, the presence of bacterial infections in pregnant women can lead increase in the risk of pregnancy outcomes especially, preterm delivery, abortion, stillbirth, and ectopic pregnancy. Therefore, it is necessary for obstetricians and gynecologists to pay attention to the diagnosis of these infections in women before pregnancy and during pregnancy in order to prevent the consequences of these infections.
PubMed: 38333348
DOI: 10.4103/ijnmr.ijnmr_199_22 -
Journal of Obstetrics and Gynaecology :... Dec 2024Vaginal bleeding during pregnancy has been recognised as a significant risk factor for adverse pregnancy outcomes. This study aimed to investigate the association... (Meta-Analysis)
Meta-Analysis Review
Vaginal bleeding during pregnancy has been recognised as a significant risk factor for adverse pregnancy outcomes. This study aimed to investigate the association between vaginal bleeding during the first trimester of pregnancy and clinical adverse effects using a systematic review and meta-analysis. Databases of Scopus, Web of Science, PubMed (including Medline), Cochrane Library and Science Direct were searched until June of 2023. Data analysis using statistical test fixed- and random-effects models in the meta-analysis, Cochran and meta-regression. The quality of the eligible studies was assessed by using the Newcastle-Ottawa Scale checklist (NOS). A total of 46 relevant studies, with a sample size of 1,554,141 were entered into the meta-analysis. Vaginal bleeding during the first trimester of pregnancy increases the risk of preterm birth (OR: 1.8, CI 95%: 1.6-2.0), low birth weight (LBW; OR: 2.0, CI 95%: 1.5-2.6), premature rupture of membranes (PROMs; OR: 2.3, CI 95%: 1.8-3.0), abortion (OR: 4.3, CI 95%: 2.0-9.0), stillbirth (OR: 2.5, CI 95%: 1.2-5.0), placental abruption (OR: 2.2, CI 95%: 1.4-3.3) and placenta previa (OR: 1.9, CI 95%: 1.5-2.4). Vaginal bleeding in the first trimester of pregnancy is associated with preterm birth, LBW, PROMs, miscarriage, stillbirth, placental abruption and placenta previa. Therefore, physicians or midwives need to be aware of the possibility of these consequences and manage them when they occur.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Stillbirth; Premature Birth; Abruptio Placentae; Placenta Previa; Placenta; Pregnancy Outcome; Abortion, Spontaneous; Uterine Hemorrhage
PubMed: 38305047
DOI: 10.1080/01443615.2023.2288224 -
Reproductive Biology and Endocrinology... Feb 2024Standard management for intrauterine lesions typically involves initial imaging followed by operative hysteroscopy for suspicious findings. However, the efficacy of... (Meta-Analysis)
Meta-Analysis
Outpatient hysteroscopy impact on subsequent assisted reproductive technology: a systematic review and meta-analysis in patients with normal transvaginal sonography or hysterosalpingography images.
BACKGROUND
Standard management for intrauterine lesions typically involves initial imaging followed by operative hysteroscopy for suspicious findings. However, the efficacy of routine outpatient hysteroscopy in women undergoing assisted reproductive technology (ART) remains uncertain due to a lack of decisive high-quality evidence. This study aimed to determine whether outpatient hysteroscopy is beneficial for infertile women who have unremarkable imaging results prior to undergoing ART.
METHODS
A systematic review and meta-analysis were conducted following PRISMA guidelines, incorporating data up to May 31, 2023, from databases such as PubMed, Embase, and the Cochrane Library. The primary outcome assessed was the live birth rate, with secondary outcomes including chemical pregnancy, clinical pregnancy rates, and miscarriage rates. Statistical analysis involved calculating risk ratios with 95% confidence intervals and assessing heterogeneity with the I statistic.
RESULTS
The analysis included ten randomized control trials. Receiving outpatient hysteroscopy before undergoing ART was associated with increased live birth (RR 1.22, 95% CI 1.03-1.45, I 61%) and clinical pregnancy rate (RR 1.27 95% CI 1.10-1.47, I 53%). Miscarriage rates did not differ significantly (RR 1.25, CI 0.90-1.76, I 50%). Subgroup analyses did not show a significant difference in clinical pregnancy rates when comparing normal versus abnormal hysteroscopic findings (RR 1.01, CI 0.78-1.32, I 38%). We analyzed data using both intention-to-treat and per-protocol approaches, and our findings were consistent across both analytical methods.
CONCLUSIONS
Office hysteroscopy may enhance live birth and clinical pregnancy rates in infertile women undergoing ART, even when previous imaging studies show no apparent intrauterine lesions. Treating lesions not detected by imaging may improve ART outcomes. The most commonly missed lesions are endometrial polyps, submucosal fibroids and endometritis, which are all known to affect ART success rates. The findings suggested that hysteroscopy, given its diagnostic accuracy and patient tolerability, should be considered in the management of infertility.
DATABASE REGISTRATION
The study was registered in the International Prospective Register of Systemic Review database (CRD42023476403).
Topics: Pregnancy; Humans; Female; Hysteroscopy; Infertility, Female; Hysterosalpingography; Fertilization in Vitro; Abortion, Spontaneous; Outpatients; Pregnancy Rate; Live Birth
PubMed: 38302947
DOI: 10.1186/s12958-024-01191-0 -
BMJ Open Jan 2024Literature surrounding the association between antidepressant use during pregnancy and miscarriage is conflicting. We aimed to conduct a systematic review and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Literature surrounding the association between antidepressant use during pregnancy and miscarriage is conflicting. We aimed to conduct a systematic review and meta-analysis of studies among pregnant women regarding the association between exposure to antidepressants during pregnancy and the risk of miscarriage, compared with pregnant women not exposed to antidepressants.
DESIGN
We conducted a systematic review and meta-analysis of non-randomised studies.
DATA SOURCES
We searched Medline, Embase and PsychINFO up to 6 August 2023.
ELIGIBILITY CRITERIA AND OUTCOMES
Case-control, cohort and cross-sectional study designs were selected if they compared individuals exposed to any antidepressant class during pregnancy to comparator groups of either no antidepressant use or an alternate antidepressant.
DATA EXTRACTION AND SYNTHESIS
Effect estimates were extracted from selected studies and pooled using a random-effects meta-analysis. Risk of bias (RoB) was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool, and heterogeneity assessed using the I statistic. Subgroup analyses were used to explore antidepressant classes and the impact of confounding by indication.
RESULTS
1800 records were identified from the search, of which 29 were included in the systematic review and meta-analysis. The total sample included 5 671 135 individuals. Antidepressant users initially appeared to have a higher risk of miscarriage compared with unexposed individuals from the general population (summary effect estimate: 1.24, 95% CI 1.18 to 1.31, I=69.2%; number of studies (n)=29). However, the summary estimate decreased when comparing against unexposed individuals with maternal depression (1.16, 1.04 to 1.31; I=58.6%; n=6), suggesting confounding by indication may be driving the association. 22 studies suffered from serious RoB, and only two of the 29 studies were deemed at moderate RoB.
CONCLUSIONS
After accounting for maternal depression, there is little evidence of any association between antidepressant use during pregnancy and miscarriage. Instead, the results indicate the biasing impact of confounding by indication.
Topics: Humans; Female; Pregnancy; Abortion, Spontaneous; Cross-Sectional Studies; Antidepressive Agents
PubMed: 38272551
DOI: 10.1136/bmjopen-2023-074600 -
Cureus Dec 2023Gestational diabetes mellitus (GDM) is the most common complication of pregnancy that arises in the 2nd and 3rd trimesters, leading to significant complications for the... (Review)
Review
Gestational diabetes mellitus (GDM) is the most common complication of pregnancy that arises in the 2nd and 3rd trimesters, leading to significant complications for the mother and her neonates, such as an increased rate of pregnancy-induced hypertension and miscarriages, while neonates may have a large birth weight, hypoglycemia, or macrosomnia. Numerous risk factors can lead to GDM; however, a significant one is polycystic ovarian syndrome (PCOS). PCOS is the most common endocrine pathology beginning before puberty, and due to significant hormonal changes, it is not diagnosed until after puberty. PCOS requires at least three of the following symptoms: hyperandrogenism, menstrual irregularities, or polycystic ovary morphology. While it is agreed that women with PCOS are at a significantly increased risk of GDM, no publication to our knowledge has evaluated the full relationship of GDM in the setting of PCOS. This paper aimed to assess this relationship and determine how it may differ for pregnant women with only GDM by determining the prevalence of GDM, the variations within phenotypes, the influence of fertilization methods, specific risk factors, maternal outcomes, and neonatal outcomes. The prevalence of GDM was significantly increased in women with PCOS compared to healthy controls, and some studies have found that phenotype A may be more likely to lead to GDM. Risk factors were similar to pregnant women with only GDM, but with GDM and PCOS specifically, preconception low sex hormone-binding globulin, increased BMI > 25 kg/m2, and preconception impaired glucose tolerance were specific. While maternal outcomes were similar to pregnant women with only GDM, women with GDM and PCOS were even more likely to develop pregnancy-induced hypertension and early miscarriage. Neonates from mothers with GDM and PCOS were more likely to have low birth weights compared to mothers with just GDM who had high birth weights. The evaluation of the relationship between GDM and PCOS allows for illumination of the need to evaluate influences that currently lack research, such as phenotype variation and influences of fertilization method. This also promotes the need to develop predictive algorithms based on risk factors to prevent these adverse outcomes for mothers and neonates.
PubMed: 38234933
DOI: 10.7759/cureus.50725 -
Journal of Clinical Medicine Dec 2023Maintenance of remission during pregnancy is vital for women with inflammatory bowel disease (IBD). The antenatal safety of novel small molecules for IBD is yet to be... (Review)
Review
Maintenance of remission during pregnancy is vital for women with inflammatory bowel disease (IBD). The antenatal safety of novel small molecules for IBD is yet to be ascertained. We aimed to describe the current evidence on reproductive data regarding small-molecule drugs. We performed a systematic review searching Embase Classic + Embase and Ovid MEDLINE for reproductive outcomes for tofacitinib, filgotinib, upadacitininb, and ozanimod. Additionally, we asked the manufacturers for available data on file regarding reproduction. We analysed data from 10 sources; six studies and four manufacturer reports were identified from our search. Significant malformation risks were reported for tofacitinib, filgotinib, upadacitininb, and ozanimod in animal studies. In 126 tofacitinib-exposed pregnancies, there were 55 live births with 2 congenital malformations and 1 serious infant infection, 14 terminations, 15 miscarriages, and 42 outcomes unknown. In 50 filgotinib-exposed pregnancies, there were 20 healthy babies, 1 congenital malformation, 9 terminations, 10 miscarriages, and 10 outcomes unknown. In 78 upadacitinib-exposed pregnancies, there were 30 healthy babies, 15 terminations, 15 miscarriages, and 18 outcomes unknown. In 60 ozanimod-exposed pregnancies, there were 31 live births with 1 congenital malformation, 1 case of intra-uterine growth restriction, 1 case of neonatal icterus, 13 terminations, 9 miscarriages, and 8 unknown outcomes. Animal data suggest significant risks of malformations for tofacitinib, filgotinib, upadacitininb, and ozanimod. Human data from clinical trials and real-world observations do not show concerning data so far, but these are very limited. Currently, alternative treatments should be used for IBD during pregnancy.
PubMed: 38202041
DOI: 10.3390/jcm13010034 -
Acta Obstetricia Et Gynecologica... May 2024Available data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pregnancy outcomes mostly refer to women contracting the infection during... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Available data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pregnancy outcomes mostly refer to women contracting the infection during advanced pregnancy or close to delivery. There is limited information on the association between SARS-CoV-2 infection in early pregnancy and outcomes thereof.
MATERIAL AND METHODS
We aimed to systematically review the maternal, fetal and neonatal outcomes following SARS-CoV-2 infection in early pregnancy, defined as <20 weeks of gestation (PROSPERO Registration 2020 CRD42020177673). Searches were carried out in PubMed, Medline, EMBASE, and Scopus databases from January 2020 until April 2023 and the WHO database of publications on coronavirus disease 2019 (COVID-19) from December 2019 to April 2023. Cohort and case-control studies on COVID-19 occurring in early pregnancy that reported data on maternal, fetal, and neonatal outcomes were included. Case reports and studies reporting only exposure to SARS-CoV-2 or not stratifying outcomes based on gestational age were excluded. Data were extracted in duplicate. Meta-analyses were conducted when appropriate, using R meta (R version 4.0.5).
RESULTS
A total of 18 studies, 12 retrospective and six prospective, were included in this review, reporting on 10 147 SARS-CoV-2-positive women infected in early pregnancy, 9533 neonates, and 180 882 SARS-CoV-2 negative women. The studies had low to moderate risk of bias according to the Newcastle-Ottawa quality assessment Scale. The studies showed significant clinical and methodological heterogeneity. A meta-analysis could be performed only on the outcome miscarriage rate, with a pooled random effect odds ratio of 1.44 (95% confidence interval 0.96-2.18), showing no statistical difference in miscarriage in SARS-CoV-2-infected women. Individual studies reported increased incidences of stillbirth, low birthweight and preterm birth among neonates born to mothers affected by COVID-19 in early pregnancy; however, these results were not consistent among all studies.
CONCLUSIONS
In this comprehensive systematic review of available evidence, we identified no statistically significant adverse association between SARS-CoV-2 infection in early pregnancy (before 20 weeks of gestation) and fetal, neonatal, or maternal outcomes. However, a 44% increase in miscarriage rate is concerning and further studies of larger sample size are needed to confirm or refute our findings.
Topics: Pregnancy; Infant, Newborn; Female; Humans; COVID-19; Abortion, Spontaneous; SARS-CoV-2; Prospective Studies; Retrospective Studies; Premature Birth; Pregnancy Complications, Infectious; Pregnancy Outcome
PubMed: 38200686
DOI: 10.1111/aogs.14764 -
Translational Andrology and Urology Dec 2023The testicular sperm instead of ejaculated sperm for intracytoplasmic sperm injection (ICSI) in infertile men with high sperm DNA fragmentation (SDF) is a controversial...
Outcomes comparison of testicular versus ejaculated sperm for intracytoplasmic sperm injection in infertile men with high DNA fragmentation: updated systematic review and meta-analysis.
BACKGROUND
The testicular sperm instead of ejaculated sperm for intracytoplasmic sperm injection (ICSI) in infertile men with high sperm DNA fragmentation (SDF) is a controversial topic. This updated systematic review and meta-analysis aims to evaluate whether couples with high level of SDF will benefit more from intracytoplasmic sperm injection with testicular sperm (Testi-ICSI) as compared to intracytoplasmic sperm injection with ejaculated sperm (Ejac-ICSI).
METHODS
A systematic search was conducted according to PRISMA guidelines, using PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL), encompassing studies from the earliest record until May 2022. We included studies analyzing comparative pregnancy outcomes of testicular versus ejaculated sperm for ICSI in infertile men with high DNA fragmentation. The risks of bias and certainty of evidence were assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, respectively.
RESULTS
Eleven studies were included. Meta-analysis showed that SDF levels revealed a significant difference association [odds ratio (OR) =-25.81; 95% confidence interval (CI): -34.82, -16.81; I=94%; P<0.00001] between testicular and ejaculated sperm. Compared with Ejac-ICSI, a non-significant tendency was observed for fertilization rates (FRs) in the Testi-ICSI group (OR =0.87; 95% CI: 0.67, 1.12; I=81%; P=0.28). However, there was significant difference pointing to better outcomes for Testi-ICSI in clinical pregnancy rates (CPRs) (OR =2.36; 95% CI: 1.71, 3.24; I=0%; P<0.00001), live birth rates (LBRs) (OR =3.10; 95% CI: 2.13, 4.51; I=4%; P<0.00001) and miscarriage rates (MRs) (OR =0.28; 95% CI: 0.13, 0.60; I=0%; P=0.001).
CONCLUSIONS
Results of this updated meta-analysis reveal that SDF rates are lower in testicular sperm than in ejaculated sperm and that Testi-ICSI is correlated with better clinical outcomes, including higher CPRs, higher LBRs, and lower MRs in infertile males with high SDF levels. Nevertheless, with the overall low to moderate quality of the studies, further well-designed controlled studies are required.
PubMed: 38196694
DOI: 10.21037/tau-23-415