Reduce Pregnancy Loss Research Articles

LMWH prevents thromboinflammation in the placenta via HBEGF-AKT signaling

AbstractLow molecular weight heparins (LMWH) are used to prevent or treat thromboembolic events during pregnancy. Although studies suggest an overall protective effect of LMWH in preeclampsia (PE), their use in PE remains controversial. LMWH may convey beneficial effects in PE independent of their anticoagulant activity, possibly by inhibiting inflammation. Here, we evaluated whether LMWH inhibit placental thromboinflammation and trophoblast NLRP3 inflammasome activation. Using an established procoagulant extracellular vesicle–induced and platelet-dependent PE-like mouse model, we show that LMWH reduces pregnancy loss and trophoblast inflammasome activation, restores altered trophoblast differentiation, and improves trophoblast proliferation in vivo and in vitro. Moreover, LMWH inhibits platelet-independent trophoblast NLRP3 (NLR family pyrin domain containing 3) inflammasome activation. Mechanistically, LMWH activates via heparin-binding epidermal growth factor (HBEGF) signaling the PI3-kinase-AKT pathway in trophoblasts, thus preventing inflammasome activation. In human PE placental explants, inflammasome activation and PI3-kinase-AKT signaling events were reduced with LMWH treatment compared with those without LMWH treatment. Thus, LMWH inhibits sterile inflammation via the HBEGF signaling pathway in trophoblasts and ameliorates PE-associated complications. These findings suggest that drugs targeting the inflammasome may be evaluated in PE and identify a signaling mechanism through which LMWH ameliorates PE, thus providing a rationale for the use of LMWH in PE.

A Comprehensive Review of the Endometrial Receptivity Array in Euploid Embryo Transfer Cycles.

The Endometrial Receptivity Array (ERA) is a revolutionary molecular diagnostic tool that determines the optimal timing for embryo transfer by analyzing the gene expression profile of endometrial tissue. This comprehensive review examines the significance and application of ERA in euploid embryo transfer cycles, where the implantation of embryos with the correct number of chromosomes is critical for achieving successful pregnancy outcomes. This review underscores its role in enhancing implantation rates and reducing pregnancy loss by assessing the evolution, methodology, clinical applications, efficacy, and challenges associated with ERA. Key findings highlight ERA's superior accuracy in identifying the window of implantation compared to traditional methods, resulting in improved clinical outcomes in assisted reproductive technology (ART) cycles. Despite its benefits, the review acknowledges challenges such as cost, accessibility, and the need for standardization. Recommendations for clinical practice emphasize the integration of ERA into routine ART protocols, comprehensive patient counseling, and the importance of multidisciplinary collaboration. The review outlines promising prospects, including technological advancements to make ERA more cost-effective, the development of refined gene expression profiles, and the potential integration with other emerging ART technologies. Further research directions include long-term studies on the outcomes of ERA-guided pregnancies and exploring its application in cases of recurrent implantation failure and unexplained infertility. Overall, ERA represents a significant advancement in reproductive medicine, offering a personalized approach to embryo transfer timing that can significantly improve the success rates of euploid embryo transfers.

Performance of preimplantation genetic testing for aneuploidy for patients with unexplained recurrent pregnancy loss and repeated implantation failure

ObjectiveThe primary objective was to investigate whether the utilization of next-generation sequencing (NGS) for preimplantation genetic testing for aneuploidy (PGT-A) could enhance the reproductive outcomes in patients with unexplained recurrent pregnancy loss (uRPL) or unexplained repeated implantation failure (uRIF) undergoing intracytoplasmic sperm injection (ICSI) cycles. Materials and methodsWe studied the reproductive outcomes of uRPL or uRIF sufferers in Chengdu women and children's central hospital from July 2020 to Jan 2024 retrospectively. These patients were categorized into two groups based on whether they underwent PGT-A or not. As the patients in the PGT-A group all had ICSI and frozen-thawed embryo transfer (FET), only patients who underwent ICSI and FET were included in the non-PGT-A group for comparison. Demographic characteristics and reproductive outcomes were compared in uRPL or uRIF sufferers. ResultsFor uRPL group, a significant increased ongoing pregnancy rate (63.6 % vs 26.1 %, p = 0.002) and reduced pregnancy loss rate (18.4 % vs 73.3 %, p < 0.001) were found in the PGT-A group in comparison with those in the non-PGT-A group. For uRIF group, no significant difference was noted in the HCG-positive rate, ongoing pregnancy rate, or pregnancy loss rate between the two groups. It is noteworthy that the maternal age in the PGT-A group was significantly higher than that in the non-PGT-A group (p = 0.048). ConclusionsNGS-based PGT-A effectively optimized the reproductive outcomes in uRPL sufferers. Although its benefits in uRIF appeared to be limited, there is a potential advantage for those with advanced maternal age. Considering the small sample size, further randomized controlled trials are warranted to validate these findings.

Maternal exposure to heat and its association with miscarriage in rural KwaZulu-Natal, South Africa: A population-based cohort study.

We sought to improve the current understanding of how climate change impacts women's reproductive health in sub-Saharan Africa. We investigated the relationship between maternal heat exposure and miscarriage (pregnancy ending before 20 weeks gestation) in a South African setting. Population-based cohort study. Our study involved data for pregnancies collected via a health and demographic surveillance system in rural KwaZulu-Natal, South Africa between 2012 and 2016. Data from the South African Weather Service were used to compute maternal exposure to heat during the following time windows for each pregnancy: during the month preceding conception (T1) and during the week preceding the study outcome (either a miscarriage or no miscarriage, T2). Heat exposure was operationalized as a continuous variable and defined as the number of days that a mother was exposed to a mean daily temperature of > 26.6°C (A "hot day," equivalent to a mean daily temperature of > 80°F) during T1 or T2. Binary logistic regression was used to investigate the relationship between maternal heat exposure and miscarriage. A total of 105/3477 pregnancies included in our analysis ended in miscarriage (3.0%). Each additional hot day during T1 was associated with a 26% higher odds of miscarriage (odds ratio: 1.26; 95% confidence interval: 1.15-1.38). No significant associations were observed between maternal heat exposure during T2 and the odds of miscarriage (odds ratio: 0.94, 95% confidence interval: 0.73-1.20). The relationship between maternal heat exposure during T1 and the odds of miscarriage was J-shaped. There is a clear relationship between maternal heat exposure during the month preceding conception and miscarriage in our sub-Saharan African setting. Given the lack of feasible strategies to reduce pregnancy loss associated with prevailing high temperatures in sub-Saharan Africa, progressive climate change will likely exacerbate existing challenges for women's reproductive health in this region.

The Effect of Human Chorionic Gonadotropin and Ketoprofen Applications on Pregnancy Rates in Dairy Cows After Artificial Insemination

The aim of the presented study is to investigate the effect of providing progesterone (P4) support for the formation and maintenance of pregnancy or suppressing the luteolysis mechanism during the maternal acceptance process on pregnancy rates. For this purpose, 96 Holstein cows, aged between 2 and 8 years, were synchronized using the Ovsynch protocol to align their estrous cycles. After artificial insemination, the cows were divided into four groups. The group receiving Human Chorionic Gonadotropn (hCG) on the 6th day after artificial insemination (H; n=20), the group receiving Ketoprofen on the evening of the 15th day and the morning of the 16th day after artificial insemination (K; n=24), the group receiving both hCG on the 6th day and Ketoprofen on the 15th day evening and 16th day morning after artificial insemination (HK; n=25), and the control group (C; n=27) that did not receive any post-insemination treatment were established. Pregnancy checks were conducted on the 30th, 45th, and 60th days through rectal and ultrasonographic (USG) examinations. According to the results of the pregnancy examinations, it was determined that 9 out of 20 cows (45.00%) in Group H, 10 out of 24 cows (41.67%) in Group K, 16 out of 25 cows (64.00%) in Group HK, and 12 out of 27 cows (44.44%) in Group C were pregnant. No statistically significant difference (P&gt;0.05) was observed among the groups. Our results suggest that a multi-purpose treatment may be required to reduce pregnancy loss during the early pregnancy period in cows due to an approximately 20% increased pregnancy rate after administering hCG and Ketoprofen. However, further studies, especially involving more cows, are necessary to optimize and use these combined treatments and potentially increase pregnancy rates.

Metroplasty increases the take-home baby rate by reducing pregnancy loss without changing the chance of conception in women with septate uterus: a retrospective, single-center, observational study

BackgroundAlthough abdominal or hysteroscopic metroplasty for septate uterus is considered to reduce pregnancy loss and increase the take-home baby (THB) rate in women with a history of recurrent pregnancy loss, there exists an inherent risk of impaired fertility. This study aimed to clarify the reproductive outcomes of women with septate uterus who underwent abdominal and hysteroscopic metroplasty in a single center.MethodsThis retrospective observational study enrolled 27 women who underwent metroplasty between 2007 and 2019. The analysis included women with septate uterus [European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) type U2)] or septate-bicornuate uterus (ESHRE/ESGE type U3b) who underwent either abdominal or hysteroscopic metroplasty. Women who did not have an immediate desire to conceive were excluded from the analysis. As a rule, we recommended pregnancy without surgery for women who had not experienced repeated pregnancy loss. Abdominal metroplasty (ABM) was performed using the modified Tompkins’ method and hysteroscopic metroplasty was performed using hysteroscopic transcervical resection of the septum [transcervical metroplasty (TCM)]. The conception ratio was calculated as the number of women who achieved ≥ 1 conception/total number of women, the pregnancy loss ratio was calculated as the number of women who experienced ≥ 1 pregnancy loss/the number of women who conceived, and the THB ratio was calculated as the number of women who achieved ≥ 1 THB/total number of women.ResultsSeventeen women underwent ABM and 10 women underwent TCM. Thirty-three conceptions and 26 babies were taken home after surgery. ABM did not change the ≥ 1 conception ratio (76% vs. 83% before and after surgery, respectively; RR = 1.08, p = 0.80). Meanwhile, ABM decreased the ≥ 1 pregnancy loss ratio (100% vs. 36%, RR = 0.36, p < 0.001) and increased the ≥ 1 THB ratio (12% vs. 71%, RR = 6.00, p < 0.01). Similarly, TCM did not change the ≥ 1 conception ratio, decreased the ≥ 1 pregnancy loss ratio, and increased the ≥ 1 THB ratio.ConclusionsBoth abdominal and hysteroscopic metroplasty for septate uterus increased the THB rate by preventing pregnancy loss without affecting the chance of pregnancy.Trial registrationNot applicable.

The effect of genetic defects on pregnancy loss in Swedish dairy cattle

The effect of carrier status of 10 lethal recessive genetic defects on pregnancy maintenance in Swedish dairy cattle was examined. The genetic defects were Ayrshire Haplotype 1, Ayrshire Haplotype 2, BTA12, BTA23, and Brown Swiss Haplotype 2 in Red Dairy Cattle (RDC), and Holstein Haplotype 1, 3, 4, 6, and 7 (HH1-HH7) in Holstein. Effects of carrier status of BTA12 and HH3 on conception rate (CR), interval from first to last service (FLS), and milk production were also examined. Data were obtained for 1,429 herds in the Swedish milk recording system, while information on carrier status of genetic defects was obtained from the Nordic Cattle Genetic Evaluation. In total, data on 158,795 inseminations in 28,432 RDC and 22,018 Holstein females were available. Data permitted separate analyses of BTA12 and HH3, but carrier frequencies of other defects were too low to enable further analysis. Pregnancy loss was defined as failure to maintain pregnancy, where pregnancy status was confirmed with manual and chemical pregnancy diagnosis, insemination, calving, sales and culling data. Odds ratios (OR) and probabilities of pregnancy loss and CR were estimated using generalized linear mixed models, while pregnancy loss, CR, FLS, milk, protein, and fat yields were analyzed using linear mixed models. Pregnancy losses were reported on average within the first month post-AI. At-risk matings were more prone to suffer pregnancy loss in BTA12 (OR = 1.79) and HH3 carriers (OR = 1.77) than not-at-risk matings. At-risk matings also had lower CR (OR = 0.62 and 0.63 for BTA12 and HH3, respectively) than not-at-risk matings. Carrier females of BTA12 had longer FLS and higher milk production than noncarriers. Conception rate and pregnancy maintenance could be improved by avoiding at-risk matings. This finding could help reduce pregnancy loss due to genetic defects in the breeding program for improved fertility.

Clinical efficacy of plasma exchange in systemic lupus erythematosus during pregnancy.

To investigate the clinical efficacy of plasma exchange (PE) with or without prednisone and hydroxychloroquine (HCQ) for the treatment of systemic lupus erythematosus (SLE) during pregnancy. The clinical characteristics of 14 pregnant women with SLE admitted to our hospital were retrospectively analyzed, including 7 only treated with prednisone and HCQ (non-PE group) as well as 7 combined PE (PE group). The delivery situations of 14 patients were recorded. Data like erythrocyte sedimentation rate (ESR), urine protein, platelet count, and SLEDAI scores were compared between two groups before treatment and 3, 6, and 12 months after delivery. Three patients in the non-PE group ended in miscarriage while all patients in the PE group were delivered successfully. Eleven successfully delivered fetuses in the two groups were healthy, and the Apgar scores were over 8. The ESR of the PE group was significantly lower than that of the non-PE group at 6 and 12 months after delivery, while there was no statistical difference in ESR between the two groups before treatment and 3 months after delivery. The ESR and urine protein were significantly higher in the non-PE group at months 3, 6, and 12 postpartum. There was a significant decrease in disease activity postpartum in the PE group compared to predelivery disease activity. The change in platelet counts between the two groups significantly increased over time in the PE group, while SLEDAI scores decreased. The combination of PE and oral prednisone and HCQ is possibly a more effective treatment than oral prednisone and HCQ alone for patients with active SLE during pregnancy. This treatment option reduces pregnancy loss and promotes the patients' postpartum condition to a certain extent.

The effectiveness and safety of intrauterine infusion of autologous regulatory T cells (Tregs) in patients with recurrent pregnancy loss and low levels of endometrial FoxP3+ cells: A retrospective cohort study.

Regulatory T cells (Tregs) are a specialized type of T cells that help maintain immune tolerance and homeostasis. The potential of Tregs cell-based therapies in treating diseases has been demonstrated in several clinical trials, which have shown promising outcomes and high safety in autoimmune diseases, transplant rejection, and graft-versus-host disease. However, their effectiveness and safety in improving endometrial receptivity and reducing pregnancy loss in human reproduction are unknown. The study used a retrospective design and included patients with recurrent pregnancy loss (RPL) and lower levels of endometrial FoxP3+ Tregs. Patients in the Tregs group (n=33) received intrauterine Tregs infusion three times during the follicular phase, while the control group (n=28) did not receive any intrauterine infusion. The intrauterine infusion of autologous Tregs increased the levels of FoxP3+ Tregs and CD56+ NK cells. Patients in the Treg group had higher live birth rates and lower miscarriage rates, especially early miscarriage rates. However, the two groups had no differences in the implantation rate, clinical pregnancy rate, and percentage of preterm delivery. The findings suggest that intrauterine Tregs infusion may be a potential therapeutic approach for RPL. Further research in larger clinical trials is needed to confirm these findings.

Uterus proliferative period ceRNA network of Yunshang black goat reveals candidate genes on different kidding number trait.

Pregnancy loss that occurs in the uterus is an important and widespread problem in humans and farm animals and is also a key factor affecting the fecundity of livestock. Understanding the differences in the fecundity of goats may be helpful in guiding the breeding of goats with high fecundity. In this study, we performed RNA sequencing and bioinformatics analysis to study the uterus of Yunshang black goats with high and low fecundity in the proliferative period. We identified mRNAs, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) by analyzing the uterine transcriptomes. The target genes of the identified miRNAs and lncRNAs were predicted, and miRNA-mRNA interaction and competitive endogenous RNA (ceRNA) networks were constructed. By comparisons between low- and high-fecundity groups, we identified 1,674 differentially expressed mRNAs (914 were upregulated, and 760 were downregulated), 288 differentially expressed lncRNAs (149 were upregulated, and 139 were downregulated), and 17 differentially expressed miRNAs (4 were upregulated, and 13 were downregulated). In addition, 49 miRNA-mRNA pairs and 45 miRNA-lncRNA pairs were predicted in the interaction networks. We successfully constructed a ceRNA interaction network with 108 edges that contained 19 miRNAs, 11 mRNAs, and 73 lncRNAs. Five candidate genes (PLEKHA7, FAT2, FN1, SYK, and ITPR2) that were annotated as cell adhesion or calcium membrane channel protein were identified. Our results provide the overall expression profiles of mRNAs, lncRNAs, and miRNAs in the goat uterus during the proliferative period and are a valuable reference for studies into the mechanisms associated with the high fecundity, which may be helpful to guide goat to reduce pregnancy loss.

Time to increase in pregnancy-specific protein B following artificial insemination is a direct determinant of subsequent pregnancy loss in lactating dairy cows

Increasing progesterone (P4) during early conceptus development may be crucial for establishment of pregnancy in dairy cattle. The objective of this study was to determine if human chorionic gonadotropin (hCG) at various times after ovulation will increase serum P4 during elongation and increase the chances for, and reduce variability to, initial increase in pregnancy-specific protein B (PSPB) following artificial insemination (AI). Time to PSPB increase was defined as the first day of increase in concentrations of PSPB between d 18 and 28 after ovulation in cows with ≥12.5% increases for 3 consecutive days compared with baseline. Lactating cows (n = 368) synchronized to Double-Ovsynch (first service) or Ovsynch (second or greater service) received one of 4 treatments: no hCG (control), or 3,000 IU of hCG on d 2 (D2), 2 and 5 (D2+5), or 5 (D5) after ovulation. All cows were examined via ultrasound on d 5 and 10 postovulation to determine percentage of cows with hCG-induced accessory CL (aCL) and to quantify and measure all luteal structures. Samples for serum P4 were collected on d 0, 5, 19, and 20 postovulation. The P4 was increased in D2, D2+5, and D5 groups compared with control. The D2+5 and D5 treatments increased aCL and P4 compared with D2 and control. The D2 treatment increased P4 on d 5 after ovulation compared with control. Serum PSPB samples were collected daily from all cows on d 18 through 28 after ovulation for determination of d of PSPB increase. Pregnancy diagnoses were performed via ultrasound examination on d 35, 63, and 100 after ovulation and AI. The D5 treatment reduced percentage of cows with, and increased the time to, PSPB increase. Primiparous cows with ipsilateral aCL had reduced pregnancy loss before d 100 postovulation compared with cows with contralateral aCL. Cows that had PSPB increase >21 d postovulation had 4× greater chances of pregnancy loss compared with cows that had PSPB increase on d 20 or 21. The highest quartile of P4 on d 5, but not on d 19 and 20, was associated with reduced time to PSPB increase. Time to PSPB increase appears to be an important measurement to understand reasons for pregnancy loss in lactating dairy cows. Increasing P4 utilizing hCG after ovulation did not enhance early pregnancy or reduce pregnancy losses in lactating dairy cows.

Mitigation of low pregnancy rate in excitable Nellore cows by administration of GnRH or P4

This research aimed to determine the effect of temperament on reproductive parameters including cortisol and progesterone (P4) in Nellore cows. Additionally, two methods for increasing plasma progesterone (P4) levels in excitable animals to enhance pregnancy rate (P/AI) and reduce pregnancy loss were investigated. In total, 939 cows were subjected to timed artificial insemination (TAI) and divided into three groups: (P4LA; n = 305) 150 mg of injectable long-acting progestogen 7 days after TAI; (GnRH; n = 306), 10 μg of buserelin acetate on day 7 after TAI; control group (CG; n = 328) without hormonal treatment. In 213 cows, randomly chosen from each group, ultrasound evaluations of the preovulatory follicle (Mode B) were performed on the day of insemination and of the corpus luteum (Color Doppler) 7 and 16 days after TAI. Blood samples were obtained from 20% of the 939 animals, randomly chosen from each group, on the day of insemination and after 7 and 16 days to measure cortisol and progesterone, respectively. At the time of insemination, subjective temperament evaluations were performed with the animals being classified as excitable (EXC) or adequate (ADQ). The SAS GLIMMIX procedure was used to compare the pregnancy rate (P/AI) and gestational loss within each temperament for the three experimental groups. Continuous variables were analyzed utilizing SAS PROC MIXED procedure. Cortisol concentration was higher and POF (preovulatory follicle) and CL (corpus luteum) volumes at the time of insemination and 7 days after AI, respectively, were lower in EXC animals than in ADQ. No significant difference was observed between the number of pixels, CL intensity, and plasma concentration of P4, 7 days after TAI. However, 16 days post-insemination, among the animals classified as EXC, higher concentrations of P4 were observed in the GnRH and P4LA groups than in the control. Regarding P4 concentrations, there was a tendency to be lower in animals classified as EXC than in ADQ within the control group (P = 0.06), while rate of blood flow from the CL was lower in EXC animals than in ADQ animals (P = 0.04). Among the ADQ animals, the GnRH and P4LA groups showed a lower CL flow rate than that observed in the control (P = 0.04), 16 days after the TAI. Among EXC animals, a higher pregnancy rate was observed in the GnRH and P4LA groups than in the control group (P = 0.01). In the control group, the pregnancy rate (P/AI) of the ADQ animals was higher than that of the EXC animals (P = 0.05). No statistically significant differences were observed between gestational losses when the treatments or temperaments were compared. In conclusion, the use of GnRH or P4LA, 7 days after insemination, improves pregnancy rates in excitable animals and is a viable alternative to minimize the negative impact of stress and improve reproductive efficiency in beef cattle.

PROGRAMAS DE INSEMINACIÓN Y TRANSFERENCIA DE EMBRIONES: EFECTO DEL CELO SOBRE LA PREÑEZ Y PÉRDIDAS EMBRIONARIAS Y FETALES EN BOVINOS

The primary objective of implementing embryo transfer in meat operations is to accelerate the rate of genetic progress in the herd. Among the main factors that affect the use of these technologies are related to the nutrition, the management and the synchronization of the estrus. As a result of research conducted in the last 20 years, the use of the receptor has increased through the application of protocols that synchronize ovulation and allow the transfer of embryos without the need for oestrus detection, generally known as fixed-time embryo transfer. (FTET). Although these protocols have functioned well for several years, attention has recently been directed to the effect of estrus expression and estradiol concentrations during pre-ovulatory follicle growth on embryonic growth and pregnancy. The experiments reviewed in this document demonstrate that oestrus expression is positively associated with high pregnancy rates and reduced pregnancy losses in recipients receiving frozen / thawed bovine embryos produced in vitro and in vivo.

O-102 Comparing the efficacy of two commercially available AI-based embryo assessment tools in a large clinical laboratory

Abstract Study question Are artificial intelligence (AI) systems an effective tool to aid in assessment of embryo viability, that can be implemented in a busy clinical laboratory setting? Summary answer LW and iDA scores both have value in predicting embryo potential, however iDA was a significantly stronger indicator of clinical pregnancy and live birth rates. What is known already Embryologist assessment of blastocysts can be variable, influenced by a range of factors including fatigue, experience, emotional bias, workload, and time pressures. An advantage of AI technologies is the consistent and objective assessment of embryos, along with the potential to observe variations not detectable by the human eye. Both AI systems have been demonstrated by their developers to have a degree of effectiveness, however there is less data to show how this translates to routine clinical use in a laboratory not involved in the development of either system. Study design, size, duration Embryos were cultured in EmbryoScope+ using Vitrolife sequential media at 6% CO2 and 5% O2. All single embryo transfers of blastocyst stage embryos during 2020 (n = 806) were assessed by two independent commercially available AI-based systems, Life Whisperer (LW) by Presagen and Intelligent Data Analysis (iDA) by Vitrolife. Both systems assessed embryos independently of embryologist assessment. Scores from LW and iDA were analysed against clinical pregnancy and birth outcomes. Participants/materials, setting, methods LW and iDA independently assigned each embryo a score from 0-10 based on prediction of embryo viability. LW scores were calculated by analysing a static 2D image of a blastocyst, input by the embryologist. iDA scores were generated from Embryoscope+ timelapse footage after a minimum of 112 hours in culture. Clinical pregnancy was defined as presence of a gestational sac, and pregnancy loss as any clinical pregnancy that did not result in live birth. Main results and the role of chance This cohort had a mean patient age of 36.9 years and had undertaken a mean of 3.2 prior cycles. The overall clinical pregnancy rate was 45.3%. Of these pregnancies, 79.2% resulted in live birth, thus the pregnancy loss rate was 20.8%. Scores at the extremes of each scale, &amp;lt;5 and ≥9, resulted in a statistically significant difference in clinical pregnancy rates from both iDA scores (24.0% and 59.3% respectively, p = 0.0001) and LW scores (38.0% and 53.1% respectively, p = 0.0031), with this difference being more pronounced in iDA assessments. When stratifying scores into five categories, a linear relationship was observed between increasing score and pregnancy rate. This relationship was consistent whether assessing by raw score, as generated by the AI program, or by allocating a designated proportion of the cohort to each category. Interestingly, pregnancy loss significantly decreased with increasing iDA scores (iDA&amp;lt;5: 50% and iDA≥9: 13.7%, p = 0.0066). Although a similar trend was seen with LW scores, this was less pronounced and not statistically significant (LW &amp;lt; 5: 28.6% and LW ≥ 9: 18.3%, p = 0.1124). This demonstrates that iDA score was both more representative of the chance of establishing a clinical pregnancy and of that pregnancy resulting in a live birth. Limitations, reasons for caution This study was conducted at a single clinical laboratory and results may not necessarily be applicable to all settings. Variables such as differing culture conditions, the transfer of multiple embryos, or transfer of embryos prior to the blastocyst stage, may impact these findings. Wider implications of the findings AI technologies may aid embryologists in the selection of embryos and reduce variability between scientists. More effective ranking of embryos may reduce the number of cycles required to achieve a pregnancy and potentially reduce pregnancy loss. This is particularly valuable to patients who have many embryos available for transfer. Trial registration number NA

P-071 Assessing the integrity of the male gamete genome to improve ART clinical outcomes

Abstract Study question Does screening for sperm chromatin fragmentation (SCF) benefit and help guide the treatment of patients with subtle male factor infertility? Summary answer In patients with abnormal SCF, an enhanced sperm selection or surgical sampling procedures improved clinical outcomes, demonstrating the value of assessing the male genome. What is known already Standard infertility workups include an assessment of the female genital tract, ovarian reserve, ovulation, and a semen analysis. Nevertheless, pregnancy failure is still encountered in couples with a young female partner with patent tubes and normal ovulation profile, and a male partner with normal semen analysis. SCF has previously been described as responsible for recurrent miscarriages and persistent ART failure. Therefore, the observed presence and degree of SCF may help guide treatment utilizing microfluidic sperm selection (MFSS) or Intracytoplasmic Sperm Injection (ICSI) with testicular spermatozoa, where in both cases, spermatozoa with higher genomic integrity were isolated, yielding improved clinical outcomes. Study design, size, duration From 2010 to 2021, we included 76 couples who had disappointing clinical outcomes; the female partners were relatively young with negative infertility workups, and the male partners had adequate semen parameters and were screened for SCF. The couples were then counseled to undergo a subsequent cycle utilizing either surgically retrieved spermatozoa or semen specimens processed by microfluidics. Clinical outcomes were measured and compared between history and post-treatment cycle(s). Participants/materials, setting, methods A total of 76 couples with poor clinical outcomes were included. Semen parameters were deemed adequate for ICSI with an average concentration of 33x106/mL and 33% motility. A minimum of 500 spermatozoa per sample were assessed by TUNEL assay with a 15% threshold. Fertilization, implantation, clinical pregnancy, delivery, and pregnancy loss rates were compared between history and post treatment cycle(s). Paired t and Chi-square tests were used to compare semen parameter and clinical outcomes, respectively. Main results and the role of chance In 168 cycles, 76 couples had poor clinical outcome results with a 67.1% fertilization rate and an 8.5% implantation rate, leading to a 16.6% clinical pregnancy rate and a 52.3% pregnancy loss rate. In these couples, testing for SCF resulted in an average DNA fragmentation of 21.6%. In efforts to reduce DNA fragmentation, 63 couples underwent microfluidics and 13 underwent surgical sperm retrieval. In an immediate post-treatment cycle, there was improvement in implantation (23.5%) (P &amp;lt; 0.001), clinical pregnancy (39.2%) (P &amp;lt; 0.01), and ongoing/delivery (37.3%) (P &amp;lt; 0.001), with a concurrent reduction in the pregnancy loss rate from 52.3% to 5.0% (P &amp;lt; 0.01). Patients were stratified according to their level of SCF. In the moderate category (15-30%, n = 60), there was meaningful improvement in implantation (24.3%) (P &amp;lt; 0.001), clinical pregnancy (40.4%) (P &amp;lt; 0.01), and ongoing/delivery rates (36.2%) (P &amp;lt; 0.001), that yielded a reduced pregnancy loss rate of 10.5% (P &amp;lt; 0.01) compared to the history cycle. In the severe SCF category (&amp;gt;30%, n = 16), there was also a meaningful improvement in implantation (15.4%), clinical pregnancy (21.7%), and ongoing/delivery rates (21.7%), as well as a reduction in the pregnancy loss rate (0%), albeit not significant. Limitations, reasons for caution In this cohort, we were able to identify a subtle male factor that was missed in the initial semen evaluation to guide treatment. However, this cohort was arbitrarily selected by the initial unexpected outcome and is a relatively small sample size. Wider implications of the findings The presence of a subtle male factor may explain disappointing clinical outcomes in some couples who have otherwise negative infertility evaluations. In these cases, screening for SCF can be a beneficial tool to help guide treatment and maximize the chances of a successful pregnancy. Trial registration number not applicable

The metabolic characteristic of decidual immune cells and their unique properties in pregnancy loss.

Maternal tolerance to semi- or fully allograft conceptus is a prerequisite for the maintenance of pregnancy. Once this homeostasis is disrupted, it may result in pregnancy loss. As a potential approach to prevent pregnancy loss, targeting decidual immune cells (DICs) at the maternal-fetal interface has been suggested. Although the phenotypic features and functions of DIC have been extensively profiled, the regulatory pathways for this unique immunological adaption have yet to be elucidated. In recent years, a pivotal mechanism has been highlighted in the area of immunometabolism, by which the changes in intracellular metabolic pathways in DIC and interaction with the adjacent metabolites in the microenvironment can alter their phenotypes and function. More inspiringly, the manipulation of metabolic profiling in DIC provides a novel avenue for the prevention and treatment of pregnancy loss. Herein, this review highlights the major metabolic programs (specifically, glycolysis, ATP-adenosine metabolism, lysophosphatidic acid metabolism, and amino acid metabolism) in multiple immune cells (including decidual NK cells, macrophages, and T cells) and their integrations with the metabolic microenvironment in normal pregnancy. Importantly, this perspective may help to provide a potential therapeutic strategy for reducing pregnancy loss via targeting this interplay.

Socio-demographic associations with pregnancy loss among Bakiga and Indigenous Batwa women in Southwestern Uganda

ObjectiveTo assess the extent of pregnancy loss (i.e., miscarriage and/or stillbirth) and examine its association with socio-demographic characteristics among Bakiga and Indigenous Batwa women in Kanungu District, southwest Uganda. MethodsAs part of a larger community-based, participatory project, a retrospective survey of maternal health histories was conducted in ten Batwa and ten Bakiga communities (n = 555 participants) collecting data on self-reported pregnancy loss (i.e., miscarriage and stillbirth) and socio-demographic characteristics. Socio-demographic associations with pregnancy loss (i.e., total miscarriages and stillbirths) were examined using multivariable Poisson and negative binomial regression. ResultsBatwa women experienced pregnancy loss more commonly than Bakiga women did (149.8/1000 vs. 96.3/1000 pregnancies). In the final adjusted model for Batwa women, being in the middle (RR 1.92; CI: 1.21–3.07) and highest (RR 1.79; CI: 1.14–2.82) wealth tertiles (compared to lowest wealth tertile) and living in Community X (RR 4.33; CI 2.27–8.28) (compared to all other communities) were associated with increased pregnancy loss. For Bakiga women, the proportion of pregnancy loss was higher for those who reported drinking alcohol during pregnancy (RR: 1.54; CI: 1.04–2.13) and being food insecure (RR 1.39; CI: 1.02–1.91). ConclusionThe proportion of, and the socio-demographic associations with, pregnancy loss differed for Bakiga and Indigenous Batwa women. These differences underscore the importance of collecting Indigenous health data to understand not only the extent of, but also the varied contextual circumstances that are associated with pregnancy loss. This nuanced and stratified information is critical for planning meaningful health programming to reduce pregnancy loss for Indigenous women.

Accessory corpus luteum regression during pregnancy II: reproductive outcomes.

The objective of this study was to evaluate the effect of accessory corpus luteum (CL) induction on fertility in dairy cows. On day 5 after artificial insemination (AI), lactating Holstein cows were assigned unequally to receive gonadotrophin-releasing hormone treatment (GnRH) (n = 641) or no treatment (control; n = 289). Cows had their blood sampled for progesterone (P4), and ovaries were scanned by ultrasound on days 5, 12, 19, 26, 33, 47, and 61 after AI. Pregnancy diagnosis was performed on days 26, 33, 47, and 61. On day 12, cows treated with GnRH were allocated to ipsilateral (n = 239) or contralateral (n = 241) groups based on the side of accessory CL formation relative to previous ovulation. Accessory CL cows had greater P4 than controls. In total, 52.7% (78/148) of pregnant cows in contralateral group had accessory CL regression earlier (<day 33; 30.8%) or later (days 33-61; 69.2%) in pregnancy with coincident decrease in P4. No cows with ipsilateral accessory CL underwent regression. There was no difference in pregnancy/AI among groups. Cows with contralateral accessory CL that underwent early regression had greater pregnancy loss (30%) than controls (10%), or cows with ipsilateral CL (3%) or contralateral CL with either later or no regression (12%). Cows with ipsilateral accessory CL had lower pregnancy loss than controls. In conclusion, elevating circulating P4 by the induction of accessory CL, particularly ipsilateral CL, increases P4 and reduces pregnancy loss. However, contralateral accessory CL that undergoes regression before day 33 of pregnancy has increased pregnancy loss, possibly due to an abrupt decrease in P4 at a pivotal period of pregnancy (days 26-33).

Combined treatment of prednisone and hydroxychloroquine may improve outcomes of frozen embryo transfer in antinuclear antibody-positive patients undergoing IVF/ICSI treatment.

The influence of anti-nuclear antibody (ANA) on induced ovulation was controversial, and the effect of prednisone plus hydroxychloroquine (HCQ) treatment on frozen embryo transfer outcomes of in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) for ANA-positive women was unclear. Fifty ANA-positive women and one-hundred ANA-negative women matched for age and anti-Mullerian hormone (AMH) were included from a Reproductive Medical Central of a University Hospital. Sixty-one oocytes pick-up (OPU) cycles in ANA+ group and one-hundred OPU cycles in ANA- group were compared; 30 frozen embryo transfer cycles without treatment and 66 with prednisone plus HCQ treatment among ANA-positive women were compared. There was no statistical difference in number of retrieved oocytes (13.66 ± 7.71 vs 13.72 ± 7.23, p = .445), available embryos (5.23 ± 3.37 vs 5.47 ± 3.26, p = .347), high-quality embryos (3.64 ± 3.25 vs 3.70 ± 3.52, p = .832), and proportion of high-quality embryos (26.5% vs. 26.7%, p = .940). Biochemical pregnancy rate (33.3% vs. 68.2%, p < .05), clinical pregnancy rate (20.0% vs. 50.1%, p < .05), and implantation rate (5.6% vs. 31.8%, p < .05) were lower, and pregnancy loss rate (83.3% vs. 23.1%, p < .05) was higher in patients with treatment than no treatment. The influence of ANA on number of retrieved oocytes, available embryos, high-quality embryos, and proration of high-quality embryos was not found. The treatment of prednisone plus HCQ may improve implantation rate, biochemical pregnancy rate, and clinical pregnancy rate, and reduce pregnancy loss rate in frozen embryo transfer outcomes for ANA-positive women.

Influence of Injectable Progesterone on the Pregnancy Rate and Gestational Loss of Nellore Females of Different Reproductive Categories Undergoing Fixed-Time Artificial Insemination

Background:Progesterone (P4) is essential for embryonic development and maintenance of pregnancy when deficiency causes early embryonic loss. In this study, we investigated the ability of hormonal supplementation to improve the fertility of cows subjected to fixed-time artificial insemination (IATF) protocols. Here, we evaluated the effect of long-acting injectable progesterone (iP4) supplementation in the D4 after IATF on pregnancy rate and pregnancy loss in Nellore cows (Bos taurus indicus) from different reproductive categories in Western Amazonia.Materials, Methods &amp; Results:Eight hundred thirteen animals from 5 farms were selected and distributed into 2 groups: control [GC; administration of 0.5 mL of 0.9% saline solution, intramuscularly – IM] (n = 407) and a group that received injectable progesterone (iP4) that was long-acting [GiP4; administration of 0.5 mL of iP4, 300 mg, via IM four days after IATF] (n = 406). Each group contained 3 subgroups: heifers, primiparous cows, and multiparous cows. Of the 407 animals in the CG, 103 were heifers, 107 primiparous, and 197 multiparous. Of the 406 animals in the GiP4 group, there were 101 heifers, 107 primiparous, and 198 multiparous. On a random day of the estrous cycle (D0), an intravaginal device containing 1 g of P4 and 2 mg of estradiol benzoate (BE) was inserted by intramuscular injection. On D8, the P4 device was removed and 150 μg of D-cloprostenol (PGF2α), 300 IU eCG, and 1 mg BE were administered IM. Cows were inseminated at D10, 48-52 h after procedure on D8. Pregnancy diagnosis was made between 35 and 40 days after insemination through ultrasound examination. Between 80 and 90 days after insemination, a new ultrasound examination was performed to assess early pregnancy loss. The data were processed using the SAS 9.2. The conception rate, pregnancy loss, and final conception rate were analyzed using PROC GLIMMIX according to groups (CG and GiP4), categories (heifers, primiparous and multiparous), and their interactions as variables. The differences in the means of least squares were adjusted using the Tukey–Kramer method. Statistical significance was defined as P &lt; 0.05. The general conception rate was 46% (375/816). Regardless of the animal class, GiP4 animals (51.97%) had higher conception rates (P &lt; 0.05) than CG (40.29%). In the subgroups (heifers, primiparous and multiparous cows), there was a difference (P &lt; 0.05) between animals treated with iP4 (52.48%, 57.94%, and 48.48%, respectively) and those who were not (39.81%, 41.12%, and 40.10%, respectively). Gestational losses, regardless of the animal class, were higher in females in the CG (7.93%) [P &lt; 0.05] compared to those in the GiP4 group (2.84%). Regardless of treatment with iP4, the percentage of gestational loss in heifers was significantly higher (10.64%) than that in primiparous and multiparous cows (3.77% and 2.86%, respectively). The final conception rates were higher in animals that received long-acting iP4, which increased the final pregnancy in all parity categories. Discussion: In the present study, the use of iP4 increased the pregnancy rate in Nellore females, regardless of the category. Although there has been no consensus on the use of iP4, there is an agreement that increases in the pregnancy rate are related to the moment of exogenous P4 application. In addition to influencing the pregnancy rate, reduction in pregnancy losses is also attributed to iP4 treatment, a fact demonstrated in the present study, where animals treated with iP4 had a lower pregnancy loss rate than normally occurs in beef cattle. Supplementation with long-acting iP4 increased the pregnancy rate at D35-40, reduced pregnancy losses, and increased the conception rate on D80-90 days in Nellore females reared in the Western Amazon, regardless of the animal category.Keywords: abortion, reproductive biotechnologies, Bos taurus indicus, pregnancy, progesterone supplementation.Descritores: aborto,biotecnologias reprodutivas, Bos taurus indicus, gestação, suplementação de progesterona.Título: Influência da progesterona injetável na taxa de prenhez e perda gestacional de fêmeas nelore de distintas categorias reprodutivas submetidas a inseminação artificial em tempo fixo.