Increased Pregnancy Loss Research Articles

Warmblood fragile foal syndrome: Pregnancy loss in Warmblood mares.

Fragile foal syndrome (FFS) or warmblood FFS Type 1 (WFFS) is a recessive, autosomal, hereditary, genetic defect causing late abortions, stillbirths and non-viable foals. Whether early pregnancy losses occur is unknown. To investigate how WFFS affects pregnancies and whether early pregnancy losses occur in WFFS matings and if there is a difference in pregnancy success between matings where both parents were allele carriers and those where only mare or stallion were WFFS carriers. Retrospective cohort study. Breeding records from a Warmblood stud farm were evaluated (2016-2019) and 2682 cycles of 177 mares analysed. Matings were assigned to four study groups, depending on the WFFS carrier status of the mare and stallion: N/WFFS × N/WFFS (n = 46), N/WFFS (mares) × N/N (n = 511), N/N × N/WFFS (stallions) (n = 191) and N/N × N/N (n = 2149). There were no differences in pregnancy rates between matings with only one WFFS carrier and those with non-carriers. When comparing N/WFFS × N/WFFS matings to those with only one or no WFFS-carrier, there were no increased pregnancy losses in the embryonic phase (day <42). By contrast, the N/WFFS × N/WFFS group had significantly more abortions (53.8%) than the other three study groups (7.9-9.2%; adjusted p < 0.0001). The higher losses were evenly distributed between the early (D42-150: 22.7% losses, n = 5) and late (D150-300: 29.4% losses, n = 5) foetal phase. The live foal rate per pregnancy for N/WFFS × N/WFFS matings was lowest (34.5%) and differed significantly (other groups 81%-84%; adjusted p < 0.0001); the peri- and postnatal mortality was higher (25%) compared with the other study groups (2.6%-3%). Low sample size in N/WWFS × N/WFFS matings, unbalanced study design, outcomes are descriptive, all mares from one stud farm. The mating of two WFFS carriers may lead to increased risks of pregnancy and foal loss.

7299 An Eucaloric High-Fat Diet Suppresses Urinary Estrogen and Progesterone Metabolites, Mimicking Reprometabolic Syndrome in Normal Weight Women

Abstract Disclosure: K. Kuhn: None. A.P. Bradford: Consulting Fee; Self; Amazon. N.F. Santoro: Advisory Board Member; Self; Menogenix, Astellas, Que Oncology, Amazon. Consulting Fee; Self; Ansh. Introduction: Reprometabolic syndrome is associated with relative hypogonadotropic hypogonadism, reduced fecundability, and increased pregnancy loss in women with obesity. We employed a eucaloric, high-fat diet (HFD) to attempt to reproduce the decreased urinary estrogen and progesterone metabolites, characteristic of this phenotype, in healthy women of normal BMI. Materials and Methods: 18 women with normal BMI (18-24.9kg/m²), mean age 29.1±6.3, were recruited for a four-month study including a prescribed 30-day, eucaloric, high-fat, dietary intervention (48% calories from fat). Women collected daily morning urine for 4 menstrual cycles. Daily urinary estrone conjugate (E1c) and pregnanediol-3-glucuronide (Pdg) levels were measured by immunoassay before, during and after the HFD. Paired t tests were used to compare average urinary E1c and Pdg levels and area under the curve (AUC) to determine the impact of the HFD. Cycles were aligned by LH peak (day 0). Results: Participants were weight stable throughout the 4 month study period with no change in BMI (pre-diet BMI 21.46±1.95 kg/m2 and post-diet BMI 21.35±1.81 kg/m2). Average mid cycle E1c peak was significantly lower during (32.4 ng/mg creatinine) and after the HFD (26.5 ng/mg creatinine), compared to pre-diet levels (43.2 ng/mg creatinine; p&amp;lt; 0.001). Post-diet urinary Pdg (AUC) was also significantly lower than pre-diet (p&amp;lt; 0.01). Follicular (days -14 to 0) and luteal phase (days 2-14) E1c AUC was significantly decreased post HFD (p&amp;lt; 0.05). Follicular and luteal phase Pdg levels were also significantly decreased post HFD (p&amp;lt;0.001, both). No significant changes in menstrual cycle length were observed throughout the study. Conclusion: Consumption of a high-fat diet for one month was sufficient to induce a significant reduction in E1c and Pdg, characteristic of Reprometabolic Syndrome of obesity, in normal weight, eumenorrheic women. This finding provides important insights regarding the mechanisms underlying reproductive dysfunction in obesity and indicates that a dietary intervention may be an effective strategy to mitigate sub-optimal reproductive hormone levels in women with obesity-related subfertility. Presentation: 6/1/2024

Impact of heat stress on female reproduction in farm animals: challenges and possible remedies

Global warming poses significant challenges to agriculture, particularly within the livestock industry. Heat stress in animals refers to the physiological and metabolic distress experienced when environmental heat causes an animal’s body temperature to exceed its thermoneutral zone. Heat stress has a significant detrimental impact on reproductive outcomes, posing a direct threat to the profitability of livestock operations. Heat stress disrupts the normal hormonal balance essential for reproduction in female livestock, adversely affecting events of folliculogenesis and embryogenesis. As a result, the developmental competence of oocytes is compromised, which is crucial for successful fertilization and reproduction. Consequently, heat stress can lead to issues such as immature oocytes, atypical or sluggish embryonic development, silent estrus, and increased pregnancy loss causing a decline in reproductive rates and livestock owners face substantial financial losses. Despite using various cooling strategies, such as water sprinkler systems, cooling shades, and cooling devices, these measures are often insufficient to restore normal reproductive rates. Therefore, it is crucial to implement and explore novel strategies to enhance reproductive efficiency during periods of heat stress. Potential mitigation techniques include estrus synchronization, artificial insemination, hormonal alterations, embryo transfer, genetic engineering, sophisticated breeding strategies, the use of nutraceuticals, and changes in management practices. This review aims to consolidate recent findings on the adverse effects of heat stress on female reproduction, especially in tropical environments, and to evaluate potential strategies for improving summer fertility of livestock. Bangladesh Journal of Animal Science 53(3): 77-100, 2024

Microbiota and Recurrent Pregnancy Loss (RPL); More than a Simple Connection.

Recurrent Pregnancy Loss (RPL) affects 1-2% of women, and its triggering factors are unclear. Several studies have shown that the vaginal, endometrial, and gut microbiota may play a role in RPL. A decrease in the quantity of Lactobacillus crispatus in local microbiota has been associated with an increase in local (vaginal and endometrial) inflammatory response and immune cell activation that leads to pregnancy loss. The inflammatory response may be triggered by gram-negative bacteria, lipopolysaccharides (LPS), viral infections, mycosis, or atypia (tumor growth). Bacterial structures and metabolites produced by microbiota could be involved in immune cell modulation and may be responsible for immune cell activation and molecular mimicry. Gut microbiota metabolic products may increase the amount of circulating pro-inflammatory lymphocytes, which, in turn, will migrate into vaginal or endometrial tissues. Local pro-inflammatory Th1 and Th17 subpopulations and a decrease in local Treg and tolerogenic NK cells are accountable for the increase in pregnancy loss. Local microbiota may modulate the local inflammatory response, increasing pregnancy success. Analyzing local and gut microbiota may be necessary to characterize some RPL patients. Although oral supplementation of probiotics has not been shown to modify vaginal or endometrial microbiota, the metabolites produced by it may benefit patients. Lactobacillus crispatus transplantation into the vagina may enhance the required immune tolerogenic response to achieve a normal pregnancy. The effect of hormone stimulation and progesterone to maintain early pregnancy on microbiota has not been adequately studied, and more research is needed in this area. Well-designed clinical trials are required to ascertain the benefit of microbiota modulation in RPL.

Ethnicity and In Vitro Fertilization Outcomes in an Equal Access to Care Setting [ID 2683634

INTRODUCTION: Many studies report racial disparities in assisted reproductive technology (ART) outcomes, specifically, lower pregnancy rates and higher miscarriage rates in Black women. In an equal access to care setting, we wanted to delineate causes of this ongoing racial disparity. METHODS: This is a retrospective review of ART cycles at Brooke Army Medical Center (BAMC) from 2013 to 2021 via the Society for Assisted Reproductive Technology database. This study received a nonresearch designation from the BAMC IRB. RESULTS: A total of 1,211 in vitro fertilization (IVF) cycles were reviewed, comparing outcomes by race from first-time embryo transfers, fresh or frozen after “freeze-all” IVF cycles. Black women (19% of all cycles) experienced a lower live birth rate (27.3% versus 34.6%; risk ratio [RR] 0.75; 95% CI 0.6–0.94), but did not experience a statistically significant increase in pregnancy loss (36.8% versus 30.6%; RR 1.26; 95% CI, 0.94–1.68] compared to all other patients. Black women were found to have a higher prevalence of uterine factor infertility (RR 2.87; 95% CI, 2.24–3.66) and tubal factor infertility (RR 1.79; 95% CI, 1.51–2.12). When controlling for uterine factor infertility, Black racial identity was no longer a risk factor for decreased live birth rate (adjusted RR 0.85; 95% CI, 0.69–1.07). CONCLUSION: Recent literature demonstrates poorer ART outcomes for Black women. Our study suggests that this may be attributable to uterine fibroids, and an increased research focus on uterine fibroid treatment in patients desiring fertility may improve ART outcomes in Black women.

Causal association between rheumatoid arthritis and pregnancy loss and intrauterine growth retardation: A bidirectional two-sample Mendelian randomization study.

To investigate the causal relationship between rheumatoid arthritis (RA) and pregnancy loss and intrauterine growth retardation (IUGR) using Mendelian randomization (MR). Genetic variants associated with RA (12,555 cases and 240,862 controls), miscarriage (1475 cases and 149,622 controls), and IUGR (3558 cases and 207,312 controls) were obtained from the FinnGen consortium, and supplementary data on RA (5201 cases and 457,732 controls) and miscarriage (7069 cases and 250,492 controls) were obtained from the Medical Research Council Integrated Epidemiology Unit (MRC-IEU). 47 Single nucleotide polymorphisms (SNPs) associated with RA were screened as instrumental variables (IV). The causal relationship between RA and pregnancy loss and IUGR were assessed by 5 MR methods, mainly inverse variance weighting (IVW). Sensitivity analyses were also performed to test the stability of the results. Bidirectional MR showed that genetically predicted RA was causally associated with pregnancy loss and IUGR in forward MR analyses, and that RA significantly increased pregnancy loss [odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.00-1.33, P = .03] and IUGR (OR = 1.08, 95% CI: 1.01-1.15, P = .019). In the reverse MR, there was no causal association between pregnancy loss (P = .15) and IUGR (P = .87) and RA. This study found a significant genetic association between RA and pregnancy loss and IUGR. RA is considered to be a high-risk factor for adverse maternal outcomes. Pre-pregnancy prophylaxis and intra-pregnancy control of patients should be emphasized to reduce the incidence of adverse pregnancy outcomes such as pregnancy loss and IUGR.

Flood exposure and pregnancy loss in 33 developing countries

Floods have affected billions worldwide. Yet, the indirect health impacts of floods on vulnerable groups, particularly women in the developing world, remain underexplored. Here, we evaluated the risk of pregnancy loss for women exposed to floods. We analyzed 90,465 individual pregnancy loss records from 33 developing countries, cross-referencing each with spatial-temporal flood databases. We found that gestational flood exposure is associated with increased pregnancy loss with an odds ratio of 1.08 (95% confidence interval: 1.04 - 1.11). This risk is pronounced for women outside the peak reproductive age range (<21 or >35) or during the mid and late-stage of pregnancy. The risk escalated for women dependent on surface water, with lower income or education levels. We estimated that, over the 2010s, gestational flood events might be responsible for approximately 107,888 (CIs: 53,944 - 148,345) excess pregnancy losses annually across 33 developing countries. Notably, there is a consistent upward trend in annual excess pregnancy losses from 2010 to 2020, and was more prominent over Central America, the Caribbean, South America, and South Asia. Our findings underscore the disparities in maternal and child health aggravated by flood events in an evolving climate.

#289 : Mitochondrial Activator BGP-15 Protects Sperm from DNA Damage During Sperm Recovery for Assisted Reproductive Technology

Background and Aims: The recovery of sperm by assisted reproductive technology (ART) results in significant DNA damage. Elevated levels of DNA damage in sperm have been linked to poor-quality embryos and increased pregnancy loss after ART. Therefore, in this study, we aimed to investigate potential of the new mitochondrial activator BGP-15 to prevent sperm DNA damage in an in vitroejaculate over time. Additionally, we sought to determine whether BGP-15 can preserve sperm quality during various sperm recovery techniques used in ART. Method: We incubated donated human semen specimens untreated or treated with BGP-15, then examined sperm motility and DNA damage (DNA fragmentation and oxidation). Semen samples were then processed using different clinical sperm recovery methods: simple wash (SW), swim-up (SU) and density gradient centrifugation (DGC); and the purified sperm underwent further analysis including motility, vitality, ROS levels, mitochondrial membrane integrity and mitochondrial membrane potential (MMP), and DNA damage. Results: Semen samples incubated with BGP-15 demonstrated improved sperm motility and reduced DNA damage levels. SW samples had the highest sperm count, while SU had the highest vitality and DNA integrity, but the lowest MMP. DGC sperm had increased MMP after BGP-15 Treatment. Although BGP-15 treatment only reduced sperm DNA fragmentation in SW samples, it reduced DNA oxidation in all recovery methods. Conclusion: Our findings indicate that clinical manipulation of patient semen samples can negatively impact sperm quality, and different sperm recovery methods have unique effects. However, the addition of BGP-15 to clinical processes can preserve sperm quality, potentially leading to improved embryo quality and ART success.

Low progesterone concentration in early pregnancy is detrimental to conceptus development and pregnancy outcome in horses

High progesterone concentrations in the early luteal phase support pregnancy, whereas subphysiological progesterone concentrations delay embryonic development at least until placentation. In this study, fetal growth and development of pregnancy was investigated in pregnancies with prostaglandin F2α-induced low progesterone concentrations (PGF) in the early luteal phase and control pregnancies (CON) in the same mares (n = 12). Mares were inseminated and in PGF pregnancies received the prostaglandin F2α analogue cloprostenol (62.5 µg) on days 0–3 after ovulation to induce subphysiological progesterone concentrations; CON pregnancies remained untreated. Mares were assigned to PGF or CON treatments in alternating order and received the opposite treatment in the following year. Blood was collected and conceptus size determined repeatedly by transrectal (≤day 101) and transabdominal (>day 101) ultrasonography. After birth, foals were weighed, measured and submitted to a clinical examination. Treatment PGF resulted in fewer pregnancies than CON treatment. All foals born from CON pregnancies were healthy and mature, whereas 4/7 PGF pregnancies were either lost (one embryonic death, one abortion) or resulted in the birth of compromised foals (P = 0.018). Size of the conceptus (e.g., diameter day 49: PGF 6.6 ± 0.7, CON 7.7 ± 0.7 cm, P = 0.006) and embryo proper (e.g., crown rump length day 54; PGF 4.4 ± 0.8, CON 5.8 ± 0.6 cm, P = 0.015) differed between treatments. These size differences decreased over time and at birth PGF foals did not differ significantly from CON foals. In conclusion, reduced progesterone concentration in the early luteal phase leads to delayed conceptus growth beyond placentation and increased pregnancy loss.

Thyroid and Pregnancy

Abstract Hormonal changes and metabolic needs during pregnancy result in profound changes in biochemical parameters of thyroid function, especially if there is preexsisting autoimmune thyroid disease (AITD). Normal thyroid function is important in order to ensure the best outcome. Many changes in the functioning of the thyroid gland occur during pregnancy, and some diseases of thyroid gland can affect both mother and fetus. Hypothyroidism is the most serious disorder that occurs during pregnancy and can go unnoticed as a „non-specific” problem. Hypothyroidism arises from the reduced ability of the gland to adapt to the increased needs during pregnancy. Mild thyroid dysfunction of mothers in the first trimester, which does not threaten during the pregnancy, can damage the psychomotor development of the child. Measurement of TSH is the most practical, simple and cost-effective screening test for thyroid dysfunction. It is necessary to apply the trimester-specific TSH reference values to correctly interpreted thyroid function during pregnancy. The presence of TPOAb is confirmation of existence of AITD, and predicts increased risk of developing subclinical hypothyroidism (SH). Preconceptional education and adequate diagnosis and treatment of thyroid dysfunction in early pregnancy are of great importance, in order to prevent complications during pregnancy and offspring. Current data indicate an increase in pregnancy loss, gestational diabetes, gestational hypertension, pre-eclampsia and preterm delivery in women with SH in pregnancy. The control of thyroid disease reduce complications of pregnancy.

Frozen embryo transfer outcomes decline with increasing female body mass index in female but not male factor infertility: analysis of 56,564 euploid blastocyst transfers

ObjectiveTo evaluate the association of body mass index (BMI) with cycle outcomes after euploid frozen blastocyst transfer. DesignRetrospective cohort study. SettingNot applicable. Patient(s)A total of 56,564 first single autologous euploid frozen embryo transfers (FET) from the 2016-2019 Society for Assisted Reproductive Technology database were analyzed by BMI and by World Health Organization BMI cohorts. Sub-analyses were performed on cycles among patients with a sole diagnosis of polycystic ovary syndrome (PCOS) (n = 4,626) and among patients with only male factor (n = 10,854). Intervention(s)None. Main outcome measure(s)Clinical pregnancy, pregnancy loss, and live birth. Results(s): Success rates and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for all outcomes were most favorable among those with normal BMI and progressively worsened with increasing BMI. These trends persisted among patients with PCOS for clinical pregnancy (aOR 0.99, 95% CI 0.98-0.997, p 0.003), pregnancy loss (aOR 1.02, 95% CI 1.01-1.04, p 0.01), and live birth (aOR 0.98, 95% CI 0.97-0.99, p <0.001), but not among patients with male factor only for clinical pregnancy (aOR 1.00, 95% CI 0.99-1.01, p 0.425), pregnancy loss (aOR 1.01, 95% CI 0.99-1.03, p 0.07), or live birth (aOR 0.99, 95% CI 0.98-1.00, p 0.08). Conclusion(s): In the largest cohort to date, increasing BMI was associated with decreased pregnancy and live birth and increased pregnancy loss following euploid FET among the entire cohort and among patients with a sole diagnosis of PCOS; however, these results were attenuated among patients with a sole diagnosis of male factor infertility, suggesting that associated female infertility diagnoses and not BMI alone may underly this trend.

Induced endometrial inflammation compromises conceptus development in dairy cattle†.

Endometrial inflammation is associated with reduced pregnancy per artificial insemination (AI) and increased pregnancy loss in cows. It was hypothesized that induced endometritis alters histotroph composition and induces inflammatory signatures on conceptus that compromise development. In Experiment 1, lactating cows were assigned to control (CON; n = 23) or to an intrauterine infusion of Escherichia coli and Trueperella pyogenes (ENDO; n = 34) to induce endometritis. Cows received AI 26days after treatment, and the uterine fluid and conceptuses were collected on day 16 after AI. In Experiment 2, Holstein heifers were assigned to CON (n = 14) or ENDO (n = 14). An embryo was transferred on day 7 of the estrous cycle, and uterine fluid and conceptuses were recovered on day 16. Composition of histotroph and trophoblast and embryonic disc gene expression were assessed. Bacterial-induced endometritis in lactating cows altered histotroph composition and pathways linked to phospholipid synthesis, cellular energy production, and the Warburg effect. Also, ENDO reduced conceptus length in cows and altered expression of genes involved in pathogen recognition, nutrient uptake, cell growth, choline metabolism, and conceptus signaling needed for maternal recognition of pregnancy. The impact of ENDO was lesser on conceptuses from heifers receiving embryo transfer; however, the affected genes and associated pathways involved restricted growth and increased immune response similar to the observed responses to ENDO in conceptuses from lactating cows. Bacterial-induced endometrial inflammation altered histotroph composition, reduced conceptus growth, and caused embryonic cells to activate survival rather than anabolic pathways that could compromise development.

Age related effect on pregnancy rate and pregnancy wastage in thoroughbred mares bred during different heat cycles postpartum under subtropical conditions

This investigation reports the correlation of age and heat cycles on the pregnancy rate and pregnancy wastage in Thoroughbred mares bred during foal heat (FH), second heat (SH) and third heat (TH) in a commercial stud farm in Kunigal, Karnataka, India. The pregnancy rate was not influenced by the different heat cycles post partum. The correlation of mare’s age on the pregnancy rate and heat cycles showed that the age of the mares significantly influenced the conception rate in mares bred during FH and TH postpartum, while it was not significant in SH. The mare’s age did not influence the pregnancy wastage significantly in mares bred during FH, SH or TH, but the FH bred mares showed significantly higher early embryonic mortality rate than SH and TH bred mares. While the abortion rate was not influenced by the different heat cycles postpartum. In conclusion, the reproductive efficiency with respect to pregnancy rate was age dependent, while pregnancy wastage looked independent of age in Thoroughbred mares bred on FH, SH and TH. The optimum age for better pregnancy rate was between 6 and 13 years in all the heat cycles and aged mares (&gt;18 years old) showed reduced pregnancy rate due to increased pregnancy losses.

Effect of repeated low doses of GnRH analogue (buserelin) on fertility performance of dairy cows with anovulation type I.

The aim of this study was to evaluate the fertility response of dairy cows with anovulation type I on repeated low doses of GnRH agonist buserelin. The study was conducted on 83 anovulatory and 60 cyclic Polish Holstein Friesian cows. Anovulation type I was defined as small ovaries with follicles of ≤ 5 mm in diameter and without corpus luteum on two examinations in a 7-10 day interval between 50-60 days after parturition. Cows from the experimental group (n=58) received 0.4 μg of buserelin i.m. once a day for 5 consecutive days. Cows from the negative control group (n = 25) received saline. Sixty cyclic cows receiving no treatment served as positive controls. Intervals from calving to estrus and from calving to conception, pregnancy rate 30-35 days and 260 days after AI, and pregnancy loss were calculated. The anovulatory cows had a substantially prolonged calving to conception interval, decreased pregnancy rate and increased pregnancy loss and culling rate compared to cyclic herd mates. The average calving to conception interval was significantly (p⟨0.05) shorter in treated cows compared to non-treated anovulatory cows (153.7 days vs 209.3 days). In conclusion, repeated low doses of GnRH analogue buserelin led to a significant shortening of calving to conception interval. More clinical trials are needed to determine the practical usefulness of this method for the treatment of anovulation type I in dairy cows.

A single-cell transcriptomic landscape of mouse testicular aging

IntroductionAdvanced paternal age of reproduction is an increasing trend, especially in developed countries and areas. This trend results in elevated risks of adverse reproductive outcomes such as reduced fertility rates, increased pregnancy loss, and poor childhood health. Yet, a systematic profiling of aging-associated molecular and cellular alterations in testicular tissue is still missing. ObjectivesWe aimed to dissect aging-associated molecular characteristics in testes of mice. MethodsSingle-cell transcriptomic sequencing and analysis were conducted in testes of young (2 months old) and old mice (24 months old). Immunofluorescences and immunochemistry were used to characterize aging-associated phenotypes and verify single cell sequence results. ResultsHere, we constructed the first single-cell transcriptomic atlases of testes of young and old mice. In-depth dissection of aging-dependent transcriptional alterations in specific cell types revealed multiple dysregulated biological processes such as increased ‘senescence-associated secretory phenotype’ and ‘inflammation’, which were major aging-associated characteristics. Further analysis of aging-related differentially expressed genes uncovered a disrupted balance of undifferentiated and differentiated spermatogonia stem cells in spermatogonia, indicative of a potential role of spermatogonia stem cells in aging-associated subfertility. Importantly, for the first time, our results identified an increased subtype of aging-specific macrophages, which may contribute to a hostile proinflammatory microenvironment during testicular aging. ConclusionTaken together, our findings depict the distinct single-cell transcriptional features of the aged mouse testes and provide enormous resources for a comprehensive understanding of the cell-type-specific molecular mechanisms underlying mouse testicular aging, which may shed light on developing novel potential diagnostic biomarkers and therapeutic targets for age-associated male subfertility.

Effects of early lactation body condition loss in dairy cows on serum lipid profiles and on oocyte and cumulus cell transcriptomes.

The objective of this study was to determine the effect of early lactation body condition (BC) loss in multiparous dairy cows on serum lipids and the effect of these changes on oocyte and cumulus cell transcriptomes. Body condition loss in dairy cattle after parturition is associated with reduced fertility and increased pregnancy loss. The complex interplay between BC, nutrition, dry matter intake, milk production, and time of calving has presented a barrier to understanding mechanisms leading to reduced fertility. We identified cows that lost BC (L group; n = 10) or maintained or gained BC (M/G group; n = 8) during the first 27 to 33 d in milk and investigated changes in serum fatty acids and oocyte and cumulus cell transcriptomes at 75 to 81 d in milk. The L group had increased serum levels of nonesterified fatty acids and mead acid, and reduced serum levels of petroselaidic acid and behenic acid. Transcriptome analyses revealed 38 differentially expressed genes (DEG) in oocytes and 71 DEG in cumulus cells of L (n = 3) compared with M/G group (n = 3). Network analysis connected serum fatty acid changes to downstream effects including reduced inflammatory response and mitochondrial membrane depolarization, increased production of reactive oxygen species, and functions related to fatty acid metabolism and cytoplasmic organization in oocytes. These effects were associated with predicted effects on signaling in oocytes through calcium, insulin, O-GlcNAcase (OGA), fibroblast growth factor receptor 4 (FGF4R), peroxisome proliferator activated receptor gamma coactivator 1 α (PPARGC1A), and phospholipase D2 (PLD2) pathways, with a connection to the cumulus cell via calcium signaling. These results connect BC loss following parturition to changes in serum lipid levels, and changes potentially affecting oocyte quality; thus, these results provide new insight into mechanism of reduced fertility.

Laparoscopic Versus Open Appendectomy during Pregnancy: Is Fetal Outcome Really Different?

Purpose: To assess maternal and fetal outcome of pregnant women with acute appendicitis underwent open versus laparoscopic appendectomy with emphasis on the pregnancy loss rate. Methods: This was a retrospective review of 116 pregnant women with acute appendicitis between 2011 and 2021 in single center, who were allocated either into open appendectomy (n=68) or laparoscopic appendectomy (n=48). Maternal and fetal outcome was recorded, tabulated and statistically analyzed. Results: There was no significant difference between both groups in terms of the rates of abortion [p&gt;0.05, OR (CI 95%) 1.47 (0.42-5.18)], intrauterine fetal demise [p&gt;0.05, OR (CI 95%) 0.94(0.2-4.39)], preterm delivery [p&gt;0.05, OR (CI 95%) 1.9(0.56-6.45)], placental abruption [p&gt;0.05, OR (CI 95%) 2.23(0.43- 11.53)], mode of delivery (p&gt;0.05) and neonatal admission to NICU (p&gt;0.05). There was no significant difference between both groups regarding perioperative data in terms of duration of symptoms before attending the hospital, final diagnosis, postoperative fever, re-operation, thromboembolism, surgical site infection and histopathology results (p&gt;0.05). Laparoscopic appendectomy was associated with shorter operative time (p&lt;0.05), shorter time for return of bowel motility (p&lt;0.001) and shorter hospital stay (p&lt;0.05). Conclusion: Laparoscopic appendectomy is safe, feasible and minimallyinvasive surgery during pregnancy and not associated with increased pregnancy loss when performed under strict criteria. Larger trials are warranted to confirm or refute these findings.

BMI and miscarriage after IVF.

To summarize recent findings related to the risk of miscarriage in women with elevated BMI undergoing IVF, and the mechanisms involved in said risk. Miscarriage rates are increased in overweight and obese women in both natural and assisted reproduction. Oocyte and embryo quality assessed according to classic morphological static parameters does not seem to be affected by excessive female body weight. Despite the initial lack of consensus between studies regarding embryo morphokinetics in obese women, blastocyst formation and quality have recently been shown to be similar across BMI groups, even in the case of euploid embryos. However, some metabolomic differences have been described in oocytes and embryos from obese women, thus pointing to a functional alteration. In women with elevated BMI, the percentage of aneuploid embryos is similar to that of normal weight women, and rates of miscarriage are higher, despite the transfer of euploid embryos. Therefore, the origin of the increased pregnancy loss rate after IVF in these women may be related to metabolomic, epigenetic or mitochondrial oocyte and embryo disturbances, or to the abnormal endocrine, metabolic and inflammatory uterine environment induced by obesity, which seems to be also responsible for other numerous complications during pregnancy and the in-utero fetal programming of postnatal diseases. A displacement of the window of implantation in obese women undergoing artificial endometrial preparation has recently been described and may be related to the poorer embryo implantation rates and increased risk of miscarriage observed following fresh and frozen embryo transfers with autologous oocytes, and with donated ova in recipients with extremely high BMI. Female obesity is related to poorer outcome in natural and assisted conception, including an increased risk of miscarriage. Embryo morphology, assessed by conventional methods or by morphokinetics, does not seem to be affected by excess weight, with similar blastocyst formation and quality than normal weight women reported in IVF cycles. Embryo aneuploidy is not increased, and higher miscarriages rates are seen after euploid embryo transfer in obese women. Disturbances of the uterus or its environment induced by female obesity seem to be the most likely cause of the increased risk of miscarriage, although metabolomic, epigenetic or mitochondrial oocyte and embryo dysfunction cannot be ruled out as cannot congenital anomalies. In the context of all the above, weight reduction before pregnancy should be advised in obese women trying to become pregnant.

Pregnancy Complications and Neonatal Mortality in a Serotonin Transporter Null Mouse Model: Insight Into the Use of Selective Serotonin Reuptake Inhibitor During Pregnancy.

Selective serotonin reuptake inhibitors (SSRI) are widely prescribed to pregnant woman. Although some SSRI compounds are known to cause pregnancy loss and fetal malformations, other SSRI continue to be used by pregnant women. However, several studies have associated the use of SSRI with adverse pregnancy outcomes: intrauterine growth restriction, preterm birth, and neonatal morbidity. Nonetheless, interpretation of studies in humans are typically complicated by the adverse pregnancy outcomes caused by depression itself. Therefore, we used a mutant mouse model with genetic ablation of the serotonin transporter, the target site for SSRI, to unravel the role of the serotonin transporter on pregnancy outcomes. The serotonin transporter null mice had increased pregnancy loss (17.5 vs. 0%), decreased number of pups born (6.6 ± 0.2 vs. 7.5 ± 0.2), and increased neonatal mortality (2.3-fold). Furthermore, preterm birth, dystocia, and fetal malformations were only observed in serotonin transporter null mice. This genetically ablated serotonin transporter mouse recapitulates several adverse pregnancy outcomes similar to those in women undergoing SSRI treatment during gestation. Additionally, neonatal loss in the present study reproduced a sudden infant death phenotype as in humans and mice with altered serotonergic signaling. In conclusion, findings from this study demonstrate a role for serotonin transporter in pregnancy maintenance and neonatal health. Additionally, it suggests that the adverse pregnancy outcomes in women taking SSRI during gestation might be due to altered serotonin transporter function caused by SSRI independent of underlying depression. This is a critical finding, given the number of women prescribed SSRI during pregnancy, and provides the framework for critical research in this area.

Assessment of the potential impacts of the Chernobyl nuclear disaster on maternal and fetal health in Hungary

Objective: Radiation exposure is known to be mutagenic and teratogenic. The aim of this study was to analyze the effects of the increased ionizing radiation emitted by the Chernobyl nuclear disaster on maternal and fetal outcomes in Hungary. Methods: A retrospective analysis of abortion, stillbirth, and congenital anomaly data for pregnancies in Hungary between 1 January 1981 and 31 December 1991 was conducted. Results: Trend analysis revealed increasing trends in spontaneous and voluntary abortion rates in Hungary during the study time period, while late pregnancy losses showed a decreasing trend. Overall, there were generally decreasing incidence rates for birth defects throughout the 1980s. Increased voluntary abortions over the study period might reflect, at least in part, maternal anxiety in the post-Chernobyl years. Decreased late pregnancy loss over the same period may be attributable to improvements in prenatal diagnostics. A notable weakness of this study is that missing data could not be complemented due to the decades that have passed since the incident. Conclusions: In conclusion, the present data suggest that the nuclear catastrophe in 1986 did not cause a significant increase in pregnancy loss or congenital malformations in Hungary.