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Discovery Immunology 2024The female reproductive tract accommodates and balances the unique immunological challenges of protection from sexually transmitted pathogens and tolerance of the fetus... (Review)
Review
The female reproductive tract accommodates and balances the unique immunological challenges of protection from sexually transmitted pathogens and tolerance of the fetus and placenta in pregnancy. Leukocytes in the female reproductive tract actively engage in extensive maternal adaptations that are imperative for embryo implantation, placental development, and fetal growth support. γδ T cells are abundant at many mucosal sites in the body, where they provide protection against pathogens and cancer, and have roles in tissue renewal and homeostasis. In this review, we summarize studies in humans and rodents showing that γδ T cells are prevalent in the female reproductive tract and fluctuate in response to hormone changes across the reproductive cycle. Emerging evidence points to a link between changes in their abundance and molecular repertoire in the uterus and pregnancy disorders including recurrent miscarriage and preterm birth. However, defining the precise functional role of female reproductive tract γδ T cells and understanding their physiological significance in reproduction and pregnancy have remained elusive. Here, we critically analyze whether reproductive tract γδ T cells could be active participants in reproductive events-or whether their principal function is immune defense, in which case they may compromise pregnancy success unless adequately regulated.
PubMed: 38863792
DOI: 10.1093/discim/kyae004 -
Cureus May 2024Background A descriptive analysis of patients who underwent various embryo transfer methods to address the root cause of their infertility at a tertiary infertility care...
Background A descriptive analysis of patients who underwent various embryo transfer methods to address the root cause of their infertility at a tertiary infertility care complex in Wardha, India, is presented herein. This analysis aims to evaluate the management of infertility and assess pregnancy outcomes. Methodology We conducted a retrospective cohort study on patients who underwent various embryo transfer methods to address the cause of their infertility, specifically focusing on a variable window of implantation (WOI) at a tertiary infertility clinic over a one-year period. The medical records of 11 patients in both the variable embryo transfer (VET) and control groups were reviewed and analyzed for this article. Results The examination of medical records revealed a significant improvement in the rate of implantation (p-value = 0.04) and clinical pregnancy outcomes (p-value = 0.03) among patients who underwent VET. Comparable statistical outcomes were observed for other variables of pregnancy outcome, including miscarriage rate, multiple pregnancy rate, and biochemical pregnancy rate. Conclusion This retrospective cohort study suggests that the utilization of VET could be a viable option for women experiencing recurrent implantation failure cycles, particularly when an adequate number of embryos are available. This is owing to the challenges in clinically diagnosing a variable WOI. Further studies with a significantly larger sample population are recommended to validate the results and integrate this approach into the standard operating procedures, aiming to enhance the likelihood of pregnancy in these populations.
PubMed: 38854330
DOI: 10.7759/cureus.60020 -
BioRxiv : the Preprint Server For... Jun 2024Rift Valley fever virus (RVFV) infection causes abortions in ruminant livestock and is associated with an increased likelihood of miscarriages in women. Using sheep and...
Rift Valley fever virus (RVFV) infection causes abortions in ruminant livestock and is associated with an increased likelihood of miscarriages in women. Using sheep and human placenta explant cultures, we sought to identify tissues at the maternal-fetal interface targeted by RVFV. Sheep villi and fetal membranes were highly permissive to RVFV infection resulting in markedly higher virus titers than human cultures. Sheep cultures were most permissive to wild-type RVFV and ΔNSm infection, while live attenuated RVFV vaccines (LAVs; MP-12, ΔNSs, and ΔNSs/ΔNSm) exhibited reduced replication. The human fetal membrane restricted wild-type and LAV replication, and when infection occurred, it was prominent in the maternal-facing side. Type-I and type-III interferons were induced in human villi exposed to LAVs lacking the NSs protein. This study supports the use of sheep and human placenta explants to understand vertical transmission of RVFV in mammals and whether LAVs are attenuated at the maternal-fetal interface.
PubMed: 38854055
DOI: 10.1101/2024.05.31.596800 -
BioRxiv : the Preprint Server For... May 2024Infection with clade I Mpox virus (MPXV) results in adverse pregnancy outcomes, yet the potential for vertical transmission resulting in fetal harm with clade IIb MPXV,...
UNLABELLED
Infection with clade I Mpox virus (MPXV) results in adverse pregnancy outcomes, yet the potential for vertical transmission resulting in fetal harm with clade IIb MPXV, the clade that is currently circulating in the Western Hemisphere, remains unknown. We established a rhesus macaque model of vertical MPXV transmission with early gestation inoculation. Three pregnant rhesus macaques were inoculated intradermally with 1.5 × 10^5 plaque forming units (PFU) of clade IIb MPXV near gestational day (GD) 30 and animals were monitored for viremia and maternal and fetal well-being. Animals were euthanized to collect tissues at 5, 14, or 25 days post-inoculation (dpi). Tissues were evaluated for viral DNA (vDNA) loads, infectious virus titers, histopathology, MPXV mRNA and protein localization, as well as MPXV protein co-localization with placental cells including, Hofbauer cells, mesenchymal stromal cells, endothelial cells, and trophoblasts. vDNA was detected in maternal blood and skin lesions by 5 dpi. Lack of fetal heartbeat was observed at 14 or 25 dpi for two dams indicating fetal demise; the third dam developed significant vaginal bleeding at 5 dpi and was deemed an impending miscarriage. vDNA was detected in placental and fetal tissue in both fetal demise cases. MPXV localized to placental villi by ISH and IHC. Clade IIb MPXV infection in pregnant rhesus macaques results in vertical transmission to the fetus and adverse pregnancy outcomes, like clade I MPXV. Further studies are needed to determine whether antiviral therapy with tecovirimat will prevent vertical transmission and improve pregnancy outcomes.
ONE SENTENCE SUMMARY
Clade IIb Mpox virus infection of pregnant rhesus macaques results in vertical transmission from mother to fetus and adverse pregnancy outcomes.
PubMed: 38853987
DOI: 10.1101/2024.05.29.596240 -
Turkish Journal of Obstetrics and... Jun 2024Hydrosalpinx impairs the success of in vitro fertilization (IVF) embryo transfer. Various surgical approaches, such as fluid aspiration or isolation of the affected...
Hysteroscopic tubal electrocoagulation versus laparoscopic tubal disconnection for the management of hydrosalpinx and subsequent pregnancy outcomes: A randomized clinical trial.
OBJECTIVE
Hydrosalpinx impairs the success of in vitro fertilization (IVF) embryo transfer. Various surgical approaches, such as fluid aspiration or isolation of the affected fallopian tubes, have been used to enhance the outcome. This study was conducted to evaluate and compare the efficacy of laparoscopic tubal disconnection (LTD) and hydroscopic tubal electrocoagulation (HTE) for hydrosalpinx before IVF.
MATERIALS AND METHODS
After obtaining ethical committee approval, we assessed 112 women who were subfertile due to hydrosalpinx to check their adherence to our selection criteria. Eligible patients were allocated into two groups (LTD vs. HTE). Both groups underwent extensive assessment before the operative procedure. IVF and subsequent embryo transfers were performed in both groups. Live birth and pregnancy rates were evaluated.
RESULTS
Patients who underwent LTD prior to IVF embryo transfer had significantly higher live birth (41%), clinical pregnancy (57%), and chemical pregnancy (61%) rates in the LTD group than in the HTE group (12%, 35%, 41%, respectively). However, we could not find a significant difference between the two groups regarding the miscarriage (17% vs. 28%, p=0.33) and multiple pregnancy (14% vs. 12%, p=0.79) rates. No major complications with HTE were observed, except for a case of uterine perforation, whereas two cases of surgical complications occurred in the LTD group. Additionally, we found a significantly shorter operative time and hospital stay (0.5±0.7 days, p=0.012) in the HTE group.
CONCLUSION
LTD may be a more effective approach compared with hysteroscopic tubal electrocoagulation for improving birth and pregnancy rates in patients with IVF and hydrosalpinx.
PubMed: 38853454
DOI: 10.4274/tjod.galenos.2024.36931 -
Journal of Obstetrics and Gynaecology... Jun 2024To identify and review factors associated with maternal deaths by suicide and drug overdose in the Canadian Coroner and Medical Examiners Database (CCMED), from...
OBJECTIVE
To identify and review factors associated with maternal deaths by suicide and drug overdose in the Canadian Coroner and Medical Examiners Database (CCMED), from 2017-2019.
METHODS
We identified potential maternal deaths in Ontario and British Columbia by searching the CCMED narratives of deaths to females 10 to 60 years old for pregnancy-related terms. Identified narratives were then qualitatively reviewed in quadruplicate to determine if they were maternal deaths by suicide or drug overdose, and to extract information on maternal characteristics, the manner of death, and factors associated with each death.
RESULTS
Of the 90 deaths identified in this study, 15 (16.7%) were due to suicide and 20 (22.2%) were due to a drug overdose. These deaths occurred to women of varying ages and across the pregnancy-postpartum period. Among the suicides, 10 were by hanging, and among the overdose-related deaths, 15 had fentanyl detected. Notably, 13 (37.1%) of the 35 deaths to suicide or drug overdose occurred beyond 42 days after pregnancy, 19 (54.3%) followed a miscarriage or induced abortion, and in 23 (65.7%) there was an established history of mental health illness. Substance use disorders were documented in 4 of the 15 suicides (26.7%), and 18 of the 20 overdose-related deaths (90.0%).
CONCLUSION
Suicide and drug overdose may contribute more to maternal deaths in Canada than previously realized. Programs are needed to identify women at risk of these outcomes, and to intervene during pregnancy and beyond the conventional postpartum period.
PubMed: 38852810
DOI: 10.1016/j.jogc.2024.102581 -
JBRA Assisted Reproduction Jun 2024This study examined whether blastocysts transferred on day 5 or day 6 of embryo development, as well as positivity for anti-thyroid peroxidase antibodies, affect...
OBJECTIVE
This study examined whether blastocysts transferred on day 5 or day 6 of embryo development, as well as positivity for anti-thyroid peroxidase antibodies, affect gestational outcomes in euthyroid women undergoing in vitro fertilisation.
METHODS
Of 428 women who underwent in vitro fertilisation assessed in this retrospective cohort study, 212 (49.5%) underwent embryo transfer on day 5 of blastulation and 216 (50.5%) on day 6. Dichotomization based on anti-thyroid peroxidase antibodies status was also performed, with 370 (86.4%) women testing negative and 58 (13.6%) testing positive. Clinical and hormonal data and rates of clinical pregnancy, miscarriage, and live births were compared between the groups.
RESULTS
When evaluating gestational outcomes based on the day of blastulation, a statistically significant difference was observed in clinical pregnancy rates [51.4% (day 5) vs. 40.7% (day 6); p=0.033]. However, there was no significant difference in the relative frequencies of miscarriages (p=1.000), live births (p=1.000), or preterm births (p=1.000). Using Cramer's V test, a weak association was found between the day of blastulation and clinical pregnancy outcomes (V2=10.7%; p=0.027). There were no statistically significant differences between the anti-thyroid peroxidase antibodies-negative and -positive groups in terms of clinical pregnancy rates (p=0.396), miscarriages (p=0.129), and live births (p=0.129).
CONCLUSIONS
Higher rates of clinical pregnancy were observed in women who underwent embryo transfers performed on day 5 compared to those on day 6. However, no effect was observed with gestational outcomes. Further, anti-thyroid peroxidase antibody positivity did not have a statistically significant impact on gestational outcomes.
PubMed: 38848251
DOI: 10.5935/1518-0557.20240036 -
Medicine Jun 2024The current research aims to investigate the relationship between Interleukin-17 (IL-17) polymorphism and the risk of recurrent pregnancy loss (RPL) within a Chinese...
The current research aims to investigate the relationship between Interleukin-17 (IL-17) polymorphism and the risk of recurrent pregnancy loss (RPL) within a Chinese population. Totally, 120 patients with RPL were selected and enrolled as the experiment group. Additionally, 210 healthy individuals undergoing routine physical examinations during the same period served as the control group. The IL-17 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism method. The IL-17 rs2275913 polymorphism exhibited 3 genotypes: GG, GA, and AA. Significant associations were observed with the AA genotype and A allele (all P < .05), indicating women with the AA genotype were 2.06 times more likely to experience RPL compared to those with the GG genotype. Similarly, women carrying the A allele faced a 1.63 times higher risk of RPL than those with the G allele. Regarding the IL-17 rs763780 polymorphism, which also presented 3 genotypes (TT, TC, CC), significant associations were noted for the CC genotype and C allele (all P < .05). Women with the CC genotype had a 1.84 times greater risk of suffering from RPL compared to those with the TT genotype, and those with the C allele were 1.51 times more likely to experience RPL than those with the T allele. The IL-17 rs2275913 and rs763780 polymorphisms contribute an increased risk to RPL in the Chinese population. Further studies, with larger sample sizes and more rigorous designs, are necessary to validate or replicate our current results.
Topics: Humans; Female; Abortion, Habitual; Interleukin-17; Adult; Genetic Predisposition to Disease; Pregnancy; China; Asian People; Polymorphism, Single Nucleotide; Case-Control Studies; Genotype; Alleles; East Asian People
PubMed: 38847697
DOI: 10.1097/MD.0000000000038333 -
Research and Practice in Thrombosis and... May 2024Paroxysmal nocturnal hemoglobinuria (PNH), a rare hematologic disease, is associated with high maternal and fetal mortality rates. Only 1 medication approved for PNH,...
BACKGROUND
Paroxysmal nocturnal hemoglobinuria (PNH), a rare hematologic disease, is associated with high maternal and fetal mortality rates. Only 1 medication approved for PNH, the complement component 5 inhibitor eculizumab, has published evidence of use during pregnancy.
KEY CLINICAL QUESTION
What were the circumstances and outcomes of the first use of pegcetacoplan, a complement component 3 inhibitor, by a pregnant woman with PNH?
CLINICAL APPROACH
The patient, with a history of 2 miscarriages and a suboptimal response to eculizumab, had hematologic improvement after switching to pegcetacoplan. She continued pegcetacoplan throughout her pregnancy. At gestational week 30, she developed abruptio placentae and breakthrough hemolysis. She delivered a normal-appearing male infant via emergency cesarean section. The breakthrough hemolysis resolved quickly with short-term intensive pegcetacoplan dosing and add-on eculizumab. To date, her laboratory values remain normal, and she has had no thromboembolic events; her son has not demonstrated growth defects.
CONCLUSION
This is the first report of pegcetacoplan treatment for PNH throughout pregnancy. The mother recovered promptly from breakthrough hemolysis that prompted an emergency delivery. Her son, who was born prematurely but healthy, has developed normally.
PubMed: 38846741
DOI: 10.1016/j.rpth.2024.102435 -
BMC Medical Genomics Jun 2024Recurrent pregnancy loss (RPL) is a common pregnancy complication that brings great pain to pregnant women and their families. Genetic factors are an important cause...
BACKGROUND
Recurrent pregnancy loss (RPL) is a common pregnancy complication that brings great pain to pregnant women and their families. Genetic factors are an important cause reason of RPL. However, clinical research on monogenic diseases with recurrent miscarriage is insufficient.
CASE PRESENTATION
Here we reported a Chinese family with RPL and genetic analysis of the abortion and parents. A paternally inherited heterozygous missense variant c.1415T > G (p.V472G) and a maternally inherited heterozygous nonsense variant c.2314del (p.M772*) in TMEM67 gene were identified by trio-exome sequencing. c.2314del (p.M772*) generated a premature stop codon and truncated protein, was classified as "pathogenic". c.1415T > G (p.V472G) located in extra-cellular region, was classified as "likely pathogenic". Biallelic variants in TMEM67 gene cause lethal Meckel syndrome 3, consistent with the proband's prenatal phenotype.
CONCLUSION
The current study of the Chinese family expands the pathogenic variant spectrum of TMEM67 and emphasizes the necessity of exome sequencing in RPL condition.
Topics: Humans; Female; Membrane Proteins; Abortion, Habitual; Pregnancy; Pedigree; Adult; Asian People; Male; Exome Sequencing; China; East Asian People
PubMed: 38844949
DOI: 10.1186/s12920-024-01902-x