-
Seminars in Reproductive Medicine Jul 2023Obesity affects nearly 40% of reproductive-aged women and has serious implications for women's overall and reproductive health. Women with an elevated body mass index... (Review)
Review
Obesity affects nearly 40% of reproductive-aged women and has serious implications for women's overall and reproductive health. Women with an elevated body mass index (BMI) have higher rates of anovulation and irregular menses, lower success with fertility treatment, and significantly higher rates of pregnancy complications, such as hypertension/preeclampsia, gestational diabetes, and preterm delivery. Many studies have also shown an association between obesity and early pregnancy loss. However, the causal association between BMI and miscarriage has not been elucidated, likely due to the multifactorial effects that BMI may have on early pregnancy development. In addition, BMI as an isolated variable fails to capture other relevant confounding health risk factors, such as nutrition, physical activity, and insulin resistance. In this review, we will summarize the current literature demonstrating the association between BMI and miscarriage, highlight the research that attempts to explain the association, and finally provide data on therapeutic interventions to improve reproductive outcomes in women suffering from obesity and early pregnancy loss.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Adult; Abortion, Spontaneous; Obesity; Risk Factors; Fertility; Infertility, Female; Body Mass Index
PubMed: 38101448
DOI: 10.1055/s-0043-1777759 -
International Journal of Molecular... May 2024This Special Issue comprises original articles in the field of clinical studies whose major topics concern the genetic and immunological aspects of miscarriage and...
This Special Issue comprises original articles in the field of clinical studies whose major topics concern the genetic and immunological aspects of miscarriage and pre-eclampsia, the isolation of decidua macrophages and Hofbauer cells in the placenta for diagnostic purposes, and epigenetic mechanisms that trigger labor [...].
Topics: Humans; Pregnancy; Female; Placenta; Abortion, Spontaneous; Reproduction; Pre-Eclampsia; Macrophages; Decidua
PubMed: 38791171
DOI: 10.3390/ijms25105132 -
JAMA Psychiatry Apr 2024Benzodiazepine use during pregnancy has raised significant concerns due to the potential harmful effects of this drug class on neonates. Studies on the association...
IMPORTANCE
Benzodiazepine use during pregnancy has raised significant concerns due to the potential harmful effects of this drug class on neonates. Studies on the association between benzodiazepine use and the risk of miscarriage are limited.
OBJECTIVE
To quantify the risk of miscarriage associated with benzodiazepine use during pregnancy after controlling for unmeasured confounders and exposure time trends.
DESIGN, SETTING, AND PARTICIPANTS
This was a nationwide, population-based case-time-control study using Taiwan's National Birth Certificate Application database and the National Health Insurance database. Pregnancies resulting in miscarriage between 2004 and 2018 were included in the case group and were 1:1 matched with exposure time-trend control individuals using disease risk score, considering demographic characteristics and prepregnancy comorbidities. Data were analyzed from August 2022 to March 2023.
EXPOSURES
Discordant exposures to benzodiazepines during risk period (1-28 days before miscarriage) and 2 reference periods (31-58 days and 181-208 days before the last menstrual period) were compared for each pregnancy.
MAIN OUTCOMES AND MEASURES
Miscarriage was defined as any pregnancy loss occurring between the first prenatal care visit (usually 8 weeks) and the 19th completed week of pregnancy.
RESULTS
This study comprised a total of 3 067 122 pregnancies among 1 957 601 women, 136 134 of which (4.4%) resulted in miscarriage. The mean (SD) age of the study population was 30.61 (5.91) years. The use of benzodiazepines during pregnancy was associated with an increased risk of miscarriage (odds ratio [OR], 1.69; 95% CI, 1.52-1.87), and consistent findings were observed across multiple sensitivity analyses considering different time windows and accounting for misclassification. In subgroup analyses, an increased risk of miscarriage was associated with each commonly used individual benzodiazepine, ranging from case-time-control ORs of 1.39 (95% CI, 1.17-1.66) for alprazolam to 2.52 (95% CI, 1.89-3.36) for fludiazepam.
CONCLUSIONS AND RELEVANCE
This nationwide case-time-control study revealed an increased risk of miscarriage associated with benzodiazepine use during pregnancy after accounting for measurable confounders, and results were unlikely to be due to unmeasured confounding. These findings underscore the necessity for health care professionals to meticulously balance the risk-benefit ratio when considering the use of benzodiazepines to treat psychiatric and sleep disorders during pregnancy.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Adult; Abortion, Spontaneous; Benzodiazepines; Risk Factors; Case-Control Studies; Risk Assessment
PubMed: 38150230
DOI: 10.1001/jamapsychiatry.2023.4912 -
Journal of Hazardous Materials Aug 2023Environmental Benzo(a)pyrene (BaP) and its ultimate metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) are typical persistent organic pollutants and endocrine...
Environmental Benzo(a)pyrene (BaP) and its ultimate metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) are typical persistent organic pollutants and endocrine disrupting chemicals. BaP/BPDE exposure might cause human trophoblast cell dysfunctions and induce miscarriage. However, the underlying mechanisms remain largely elusive. In this study, we found that BPDE exposure induced human trophoblast cell pyroptosis by up-regulating NLRP3/Caspase1/GSDMD pathway. We also identified that lnc-HZ14 was highly expressed in BPDE-exposed trophoblast cells and in recurrent miscarriage (RM) vs healthy control (HC) villous tissues. Lnc-HZ14 promoted trophoblast cell pyroptosis by promoting IRF1-mediated ZBP1 transcription, increasing METTL3-mediated m6A methylation on NLRP3 mRNA and its stability, and also enhancing ZBP1/NLRP3 protein interactions. Knockdown of lnc-HZ14/ZBP1/NLRP3 axis could efficiently alleviate BPDE-induced trophoblast cell pyroptosis. Higher level of pyroptosis, as indicated by the up-regulation of lnc-HZ14/ZBP1/NLRP3 axis, was found in RM vs HC villous tissues. In BaP-exposed mouse model, BaP exposure induced placental tissue pyroptosis and miscarriage by up-regulating murine Zbp1/Nlrp3 axis, and knockdown of Nlrp3 could efficiently reduce placenta pyroptosis and alleviate BaP-induced mouse miscarriage. Serum IL-1β protein level might act as a promising indicator to predict the risk of miscarriage. These findings provided new insights into BaP/BPDE-induced trophoblast cell pyroptosis and miscarriage and might be helpful for further assessment of the toxicological effects of BaP/BPDE on the female reproduction.
Topics: Pregnancy; Humans; Female; Mice; Animals; 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Trophoblasts; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; Abortion, Spontaneous; Benzo(a)pyrene; Placenta; Methyltransferases; RNA-Binding Proteins
PubMed: 37167865
DOI: 10.1016/j.jhazmat.2023.131543 -
Fertility and Sterility Nov 2023The physical and psychological impact of miscarriage can be devastating. There are many lifestyle and therapeutic interventions that may prevent a miscarriage. In this... (Review)
Review
The physical and psychological impact of miscarriage can be devastating. There are many lifestyle and therapeutic interventions that may prevent a miscarriage. In this review, we have outlined the key areas for health optimization to prevent pregnancy loss, drawing on the most up-to-date evidence available. The 3 key areas identified are lifestyle optimization in women, lifestyle optimization in men, and therapeutic interventions. The evidence demonstrates that the treatments to consider are first-trimester progesterone administration, levothyroxine in women with subclinical hypothyroidism, and the combination of aspirin and heparin in women with antiphospholipid antibodies.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Abortion, Habitual; Aspirin; Heparin; Thyroxine; Hypothyroidism
PubMed: 37648141
DOI: 10.1016/j.fertnstert.2023.08.955 -
Seminars in Reproductive Medicine Jul 2023Obesity is a highly prevalent chronic disease with a significant effect on reproductive-age women. The clinical implications of obesity on fertility and pregnancy are... (Review)
Review
Obesity is a highly prevalent chronic disease with a significant effect on reproductive-age women. The clinical implications of obesity on fertility and pregnancy are well studied citing ovulatory dysfunction, hormonal imbalances, higher miscarriage rates, and increased maternal and neonatal risks. For this reason, many patients with obesity seek reproductive specialists to help build their families. Despite this literature base, the effect of weight loss interventions prior to assisted reproductive technology (ART) is lacking. This review aims to outline the impact of obesity on ART, specifically in vitro fertilization (IVF). Response differences to treatment protocols compared with normal weight counterparts, limitations of access to care, and the mixed results of weight-reduction strategies prior to fertility treatment will be addressed. The known data surrounding benefits of lifestyle modification, pharmacologic therapies, and surgical interventions for obesity prior to IVF are outlined and found to emphasize a need for further research to determine the optimal approach for infertility patients with obesity.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Obesity; Fertilization in Vitro; Infertility; Fertility; Abortion, Spontaneous
PubMed: 37913788
DOI: 10.1055/s-0043-1776420 -
Fertility and Sterility Nov 2023To understand the clinical risks associated with the transfer of embryos classified as a mosaic using preimplantation genetic testing for aneuploidy.
OBJECTIVE
To understand the clinical risks associated with the transfer of embryos classified as a mosaic using preimplantation genetic testing for aneuploidy.
DESIGN
Analysis of data collected between 2017 and 2023.
SETTING
Multicenter.
PATIENTS
Patients of infertility treatment.
INTERVENTION
Comparison of pregnancies resulting from embryos classified as euploid or mosaic using the 20%-80% interval in chromosomal intermediate copy numbers to define a mosaic result.
MAIN OUTCOME MEASURES
Rates of spontaneous abortion, birth weight, length of gestation, incidence of birth defects, and chromosomal status during gestation.
RESULTS
Implanted euploid embryos had a significantly lower risk of spontaneous abortion compared with mosaic embryos (8.9% [n = 8,672; 95% confidence interval {CI95} 8.3, 9.5] vs. 22.2% [n = 914; CI95 19.6, 25.0]). Embryos with mosaicism affecting whole chromosomes (not segmental) had the highest risk of spontaneous abortion (27.6% [n = 395; CI95 23.2, 32.3]). Infants born from euploid, mosaic, and whole chromosome mosaic embryos had average birth weights and lengths of gestation that were not statistically different (3,118 g and 267 days [n = 488; CI95 3,067, 3,169, and 266, 268], 3052 g and 265 days [n = 488; CI95 2,993, 3,112, and 264,267], 3,159 g and 268 days [n = 194; CI95 3,070, 3,249, and 266,270], respectively). Out of 488 infants from mosaic embryo transfers (ETs), one had overt gross abnormalities as defined by the Centers for Disease Control and Prevention. Most prenatal tests performed on pregnancies from mosaic ETs had normal results, and only three pregnancies produced prenatal test results reflecting the mosaicism detected at the embryonic stage (3 out of 250, 1.2%; CI95 0.25, 3.5).
CONCLUSION
Although embryos classified as mosaic experience higher rates of miscarriage than euploid embryos (with a particularly high frequency shortly after implantation), infants born of mosaic ETs are similar to infants of euploid ETs. Prenatal testing indicates that mosaicism resolves during most pregnancies, although this process is not perfectly efficient. In a small percentage of cases, the mosaicism persists through gestation. These findings can serve as risk-benefit considerations for mosaic ETs in the fertility clinic.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Abortion, Spontaneous; Preimplantation Diagnosis; Fertilization in Vitro; Blastocyst; Genetic Testing; Aneuploidy; Mosaicism; Chromosomes
PubMed: 37532168
DOI: 10.1016/j.fertnstert.2023.07.022 -
Fertility and Sterility Nov 2023Approximately 80% of miscarriages happen within the first 12 weeks of gestation. More than half of early losses result from genetic defects, usually presenting as... (Review)
Review
Approximately 80% of miscarriages happen within the first 12 weeks of gestation. More than half of early losses result from genetic defects, usually presenting as abnormal chromosome numbers or gene rearrangements in the embryo. However, the impact of genetics on pregnancy loss goes well beyond embryonic aneuploidy. For example, the use of big data has recently led to the discovery of specific gene mutations that may be implicated in sporadic and recurrent miscarriages. Further, emerging data suggest that genetic factors play a role in conditions for which there is a causative association with recurrent pregnancy loss. Here, we summarize the evidence on the genetics of miscarriage and provide an overview of the diagnosis and prevention of genetic causes associated with sporadic and recurrent pregnancy loss.
Topics: Pregnancy; Female; Humans; Abortion, Habitual; Chromosome Aberrations; Aneuploidy; Mutation; Embryo, Mammalian
PubMed: 37648143
DOI: 10.1016/j.fertnstert.2023.08.952 -
Human Reproduction (Oxford, England) Nov 2023Can potential mechanisms involved in the likely concurrence of diminished ovarian reserve (DOR) and miscarriage be identified using genetic data?
STUDY QUESTION
Can potential mechanisms involved in the likely concurrence of diminished ovarian reserve (DOR) and miscarriage be identified using genetic data?
SUMMARY ANSWER
Concurrence between ovarian reserve and spontaneous miscarriage was observed, and may be attributed to shared genetic risk loci enriched in antigen processing and presentation and autoimmune disease pathways.
WHAT IS KNOWN ALREADY
Previous studies have shown that lower serum anti-Müllerian hormone (AMH) levels are associated with increased risk of embryo aneuploidy and spontaneous miscarriage, although findings have not been consistent across all studies. A recent meta-analysis suggested that the association between DOR and miscarriage may not be causal, but rather a result of shared underlying causes such as clinical conditions or past exposure. Motivated by this hypothesis, we conducted the present analysis to explore the concurrence between DOR and miscarriage, and to investigate potential mechanisms using genetic data.
STUDY DESIGN, SIZE, DURATION
Three data sources were used in the study: the clinical IVF data were retrospectively collected from an academically affiliated Reproductive Medicine Center (17 786 cycles included); the epidemiological data from the UK Biobank (UKB), which is a large-scale, population-based, prospective cohort study (35 316 white women included), were analyzed; and individual-level genotype data from the UKB were extracted for further analysis.
PARTICIPANTS/MATERIALS, SETTING, METHODS
There were three modules of analysis. First, clinical IVF data were used to test the association between ovarian reserve biomarkers and the subsequent early spontaneous miscarriage risk. Second, the UKB data were used to test the association of spontaneous miscarriage history and early menopause. Third, individual-level genotype data from the UKB were analyzed to identify specific pleiotropic genes which affect the development of miscarriage and menopause.
MAIN RESULTS AND THE ROLE OF CHANCE
In the analysis of clinical IVF data, the risk of early spontaneous miscarriage was 1.57 times higher in the group with AMH < 1.1 ng/ml group (P < 0.001), 1.62 times for antral follicular count <5 (P < 0.001), and 1.39 times for FSH ≥10 mIU/ml (P < 0.001) in comparison with normal ovarian reserve groups. In the analysis of UKB data, participants with a history of three or more miscarriages had a one-third higher risk of experiencing early menopause (odds ratio: 1.30, 95% CI 1.13-1.49, P < 0.001), compared with participants without spontaneous miscarriage history. We identified 158 shared genetic risk loci that affect both miscarriage and menopause, which enrichment analysis showed were involved in antigen processing and presentation and autoimmune disease pathways.
LIMITATIONS, REASONS FOR CAUTION
The analyses of the UKB data were restricted to participants of European ancestry, as 94.6% of the cohort were of white ethnicity. Further studies are needed in non-white populations. Additionally, maternal age at the time of spontaneous miscarriage was not available in the UKB cohort, therefore we adjusted for age at baseline assessment in the models instead. It is known that miscarriage rate in IVF is higher compared to natural conception, highlighting a need for caution when generalizing our findings from the IVF cohort to the general population.
WIDER IMPLICATIONS OF THE FINDINGS
Our findings have implications for IVF clinicians in terms of patient counseling on the prognosis of IVF treatment, as well as for genetic counseling regarding miscarriage. Our results highlight the importance of further research on the shared genetic architecture and common pathophysiological basis of DOR and miscarriage, which may lead to new therapeutic opportunities.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by the Hunan Youth Science and Technology Innovation Talent Project (2020RC3060), the International Postdoctoral Exchange Fellowship Program (Talent-Introduction Program, YJ20220220), the fellowship of China Postdoctoral Science Foundation (2022M723564), and the Natural Science Foundation of Hunan Province, China (2023JJ41016). This work has been accepted for poster presentation at the 39th Annual Meeting of ESHRE, Copenhagen, Denmark, 25-28 June 2023 (Poster number: P-477). The authors declare no conflict of interest.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Pregnancy; Humans; Female; Adolescent; Abortion, Spontaneous; Retrospective Studies; Prospective Studies; Ovarian Reserve; Ovarian Diseases; Menopause, Premature; Anti-Mullerian Hormone; Autoimmune Diseases; Fertilization in Vitro
PubMed: 37713654
DOI: 10.1093/humrep/dead180 -
Clinical Obstetrics and Gynecology Dec 2023In 2019, the US Centers for Disease Control reported that 7% of abortions were performed after 13 weeks of pregnancy, a small proportion of all terminations. However,...
In 2019, the US Centers for Disease Control reported that 7% of abortions were performed after 13 weeks of pregnancy, a small proportion of all terminations. However, the need for second-trimester abortions will increase commensurate with restrictions to access nationwide. Second-trimester abortions are performed with medications or through a procedure. Health care practitioners serving persons at risk of pregnancy should understand how abortions are performed and how to deliver evidence-based postabortion care. The purpose of this article is to provide a foundation for caring for individuals before, during, and after second-trimester abortion.
Topics: Pregnancy; Female; Humans; Pregnancy Trimester, Second; Abortion, Induced; Abortion, Spontaneous
PubMed: 37910075
DOI: 10.1097/GRF.0000000000000825