Miscarriage Rate Research Articles

A systematic review and meta-analysis of double trophectoderm biopsy and/or cryopreservation in PGT: balancing the need for a diagnosis against the risk of harm.

To prevent the transfer of embryos affected by monogenic conditions and/or chromosomal defects, preimplantation genetic testing (PGT) requires trophectoderm biopsy and cryopreservation. In 2-6% of biopsies, the diagnosis may be inconclusive due to DNA amplification failure or low-quality results. In these cases, a round of re-warming, re-biopsy, and re-cryopreservation is required to obtain a genetic diagnosis. In other cases, when the IVF centre starts providing PGT and/or when the patients develop an indication because of multiple failures, miscarriages or the birth of an affected child after IVF, cryopreserved untested embryos may be warmed, biopsied, and then re-vitrified. However, it is still unclear whether multiple manipulations may reduce reproductive outcomes after PGT. This study aimed at conducting a systematic review to investigate the available evidence on the safety of double biopsy and/or double cryopreservation-warming and provide recommendations in this regard. We performed meta-analyses of the differences in the reproductive outcomes (live birth per embryo transfer [LBR per ET], clinical pregnancy rate per ET [CPR per ET], and miscarriage rate per clinical pregnancy [MR per CP]) in double cryopreservation and single biopsy (CBC) or double biopsy and double cryopreservation (BCBC) flows vs the control single biopsy and single cryopreservation (BC) flow. Cryo-survival rates before ET and gestational and perinatal outcomes were also reported. PRISMA guidelines were followed to gather all available information from the literature (PubMed, Scopus, and Embase). We used Medical Subject Headings (MeSH) terms and a list of specific keywords relevant for the study question. We searched for original studies in humans, published in peer-reviewed journals in English up to April 2024. Four independent authors assessed the articles for inclusion. One included paper was retrieved from another source. A total of 4219 records were identified, and 10 studies were included in the meta-analysis. Certainty of evidence level ranged from low to moderate. Both the CBC and BCBC groups showed reduced reproductive outcomes compared to the control (BC). Specifically, live birth rates per embryo transfer were lower in the CBC group (OR: 0.56, 95% CI: 0.38-0.81, I2 = 58%; six studies) and the BCBC group (OR: 0.51, 95% CI: 0.34-0.77, I2 = 24%; six studies). CPR per ET were also lower in the CBC group (OR: 0.68, 95% CI: 0.51-0.92, I2 = 57%; seven studies) and the BCBC group (OR: 0.60, 95% CI: 0.46-0.78, I2 = 0%; seven studies). Additionally, MR per CPs were higher in both the CBC group (OR: 1.68, 95% CI: 1.02-2.77, I2 = 50%; seven studies) and the BCBC group (OR: 2.08, 95% CI: 1.13-3.83, I2 = 28%; seven studies). Cryo-survival as well as gestational and perinatal outcomes were within the expected norms in the studies reporting them. Improved genetic technologies, standardization of laboratory protocols, operators' proficiency with biopsy and cryopreservation, and continuous monitoring of the performance are essential to minimize inconclusive diagnoses and the putative impact of additional embryo manipulations. Although poorer reproductive outcomes might result from double biopsy and/or double cryopreservations, these practices may still be worthwhile to avoid transferring affected/aneuploid blastocysts. Therefore, the risks must be weighed against the potential benefits for each specific couple. PROSPERO (ID: CRD42024503678).

Intracytoplasmic sperm injection compared with in vitro fertilisation in patients with non-male factor infertility with low oocyte retrieval: a single-centre, retrospective cohort study

ObjectiveTo investigate the effects of in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) on the clinical outcomes of non-male factor patients aged >35 with three or fewer oocytes retrieved.DesignRetrospective...

Subsequent Pregnancy Outcomes Following Prepregnancy Cerclage in Patients with Absent Ecto-Cervix

Background: We aimed to determine whether the prepregnancy cerclage for women with cervical incompetence with absent ecto‑cervix affects the time from surgery to conception and subsequent pregnancy outcome. Methods: This retrospective study was carried out on patients with at least one previous history of second-trimester abortion and extremely short cervix found by gynecological examination. A total of 40 cases of McDonald's cerclage before pregnancy were performed. The time from surgery to conception and pregnancy outcome were followed up for 4 years. The main outcomes were the time from surgery to conception, and the gestational week of delivery, miscarriage rate, preterm delivery rate. Results: Between September 2018 and December 2022, 37 women became pregnant following prepregnancy cerclage. In total, 36 babies were born to 37 mothers. The recurrence rate of second-trimester miscarriage was 8.11% (3/37) and the preterm birth rate was 29.73% (11/37). Mean time from surgery to conception was 38w (range 2w-160w).Mean gestational age at delivery was 36 weeks +4 (256 days).The live birth rate was 100%. There were no maternal complications, no intestinal and bladder injuries. Conclusion: Cervical incompetence patients with absent ecto‑cervix may benefit from prepregnancy cerclage without affecting the interpregnancy interval.

Correlation Between Luteal Phase Serum Progesterone Levels and Pregnancy Outcome in Frozen Embryo Transfer Cycles: A Prospective Cohort Study

Objectives To study the correlation between luteal phase serum progesterone (P4) levels and pregnancy outcome in frozen embryo transfer (FET) cycles and to find out the cut-off level of luteal phase serum P4 which favours successful pregnancy outcome in FET cycles. Material and Methods This prospective cohort study included 100 women undergoing hormone replacement therapy (HRT)-FET cycle at Akanksha IVF Centre from December 2023 to June 2024, fulfilling the inclusion and exclusion criteria. Serum P4 levels were measured for all the patients in the luteal phase (days 21–23) after FET with intramuscular P4 as luteal phase support. Pregnancy outcome was assessed in terms of implantation rate, biochemical pregnancy rate, clinical pregnancy rate (CPR), first-trimester miscarriage rate and ongoing pregnancy rate. Results The most favourable pregnancy outcomes were observed at serum P4 levels 25.1-35 ng/mL. A statistically significant association was seen between the luteal phase serum P4 levels and implantation rate (36.08%), biochemical pregnancy rate (4%), CPR (52%) and ongoing pregnancy rate (42%). According to the receiver operating characteristic (ROC) curve analysis, the optimal cut-off value for favourable outcomes was determined to be 22.3 ng/mL. However, the analysis also indicated that the luteal phase serum P4 levels did not reliably predict clinical or ongoing pregnancy. Conclusion Larger studies are needed to establish a threshold level of serum P4 in the luteal phase that can differentiate between successful and unsuccessful implantation. However, it is still uncertain whether the issue of unsuccessful implantation can be resolved once it is detected on days 21–23 of the HRT-FET cycle.

Enhanced Prenatal and Postnatal Development Study in Marmoset Monkeys Following Administration of Felzartamab.

Felzartamab is a recombinant fully human immunoglobulin G1 anti-CD38 monoclonal antibody under clinical investigation for immune-mediated diseases. In support of felzartamab clinical development, toxicology studies were conducted in marmoset monkeys, which was the most relevant species based on CD38 binding affinity, pharmacologic activity, and target expression. The felzartamab toxicology program included an enhanced prenatal and postnatal development (ePPND) study to identify potential reproductive and postnatal development risks. In this ePPND study, pregnant marmoset monkeys were randomized to receive vehicle (0mg/kg) or felzartamab at two dose levels (15mg/kg and 75mg/kg) twice per week until parturition, and maternal animals and infants were evaluated for 6 months thereafter. Felzartamab exposure was confirmed in maternal animals and infants in both dosing groups. Overall, felzartamab was well tolerated by pregnant animals at the evaluated doses, with no effect on body weight or body weight gain during pregnancy. No felzartamab-related effects on pregnancy loss or stillbirth rate were observed, and litter counts and numbers of liveborn infants were similar between the vehicle and felzartamab groups. Among infants, there were no felzartamab-related malformations or variations in external anatomy or skeletal morphology and no felzartamab-related observations in histopathology, hematologic and immune cell development, or humoral immune response to vaccination. In conclusion, among pregnant marmoset monkeys dosed with felzartamab, the lack of reproductive toxicity and felzartamab-related effects on offspring supports the clinical evaluation of felzartamab in women of childbearing potential and further demonstrates the suitability of the marmoset monkey for ePPND studies.

Severe alcohol withdrawal during pregnancy or early postpartum: maternal and fetal outcomes.

Alcohol withdrawal syndrome (AWS) during pregnancy is under-researched despite growing concerns about increased alcohol use among pregnant women. This study aims to explore the severity of AWS and its impact on maternal and fetal outcomes. This retrospective study reviewed the medical records of patients admitted to the Mayo Clinic who underwent the CIWA-Ar protocol for AWS from June 2019 through June 2022. Pregnant women identified in this cohort had their pregnancy, labor, and neonatal data analyzed for alcohol-related complications and outcomes. Out of the medical records reviewed, 8 cases involved pregnant women experiencing AWS. These cases showed a high severity of withdrawal symptoms, with a median peak CIWA-Ar score of 17 (IQR = 14). Maternal complications included a high rate of ICU admissions (37.5%; n = 3) and significant rates of miscarriage and stillbirth (37.5%; n = 3). Fetal outcomes were concerning, with 1 out of 5 (20%) neonates requiring NICU admission and experiencing conditions such as respiratory failure and neonatal abstinence syndrome. Developmental problems were noted in 2 out of 5 (40%) newborns. The findings highlight the severe implications of AWS during pregnancy, impacting both maternal and fetal health. The severity of AWS requires attentive clinical management and preventative interventions. Future research should focus on larger, prospective studies to better understand and address the risks associated with AWS in pregnant women and to improve health outcomes for mothers and their children. • Severe AWS during pregnancy leads to high ICU admissions and adverse neonatal outcomes. • 37.5% of pregnant women with AWS experienced miscarriage or stillbirth. • 20% of newborns from mothers with AWS required NICU admission for serious conditions; 40% of newborns had developmental problems. • Findings underscore the need for specialized treatment protocols to improve outcomes for pregnant women and their newborns.

A statewide system for maternal-infant linked longitudinal surveillance: Indiana's model for improving maternal and child health

Indiana, located in the Midwest region of the United States, faces significant challenges with respect to health, especially maternal and child health (MCH). These challenges include high rates of stillbirth, neonatal abstinence syndrome (NAS) and congenital syphilis (CS). Not only are these often-fatal conditions underreported, but it can also be difficult to track them longitudinally, as mothers and infants are not routinely linked through electronic health records (EHRs). This paper describes the process, structure and planned outcomes of a partnership between Indiana University, Regenstrief Institute and public health partners in support of the U.S. Centers for Disease Control and Prevention's Pregnant People-Infant Linked Longitudinal Surveillance (PILLARS) program. Together, academic, clinical and public health organisations are collaboratively developing an infrastructure and deploying novel methods to surveil stillbirth, CS and NAS longitudinally. The infrastructure includes: (a) deploying deterministic and probabilistic algorithms to link mothers and their infants using multiple, linked data sources; (b) creating and maintaining a registry of maternal-infant dyads; (c) using the registry to perform longitudinal surveillance in collaboration with Indiana public health authorities on stillbirth, NAS and CS and (d) translating information from surveillance activities into action by collaborating with public health and community-based organisations to improve and implement prevention activities in vulnerable Indiana communities. Our long-term goal is to improve outcomes for these conditions and other priority MCH outcomes by expanding our work to additional MCH use cases.

The effect of an enhanced fetal growth ultrasound protocol on pregnancy outcomes: A retrospective service evaluation within a single UK National Health Service centre between 2014 and 2022

Aim: Growth Assessment Protocol is a fetal growth initiative designed to improve antenatal detection of babies who are small-for-gestational-age and reduce stillbirths. However, its direct impact on pregnancy outcome and stillbirth rates is questioned. This service evaluation aimed to assess Growth Assessment Protocol’s influence on pregnancy outcomes at a National Health Service hospital. Method: Anonymous, maternity and ultrasound data, routinely acquired between 2014 and 2022 were extracted from clinical databases (Viewpoint, Euroking). Trends in maternity data and ultrasound scan volume were explored with descriptive statistics. Variables of stillbirth, antenatal small-for-gestational-age detection and scan volume were compared before and after Growth Assessment Protocol implementation. Associations between these variables were evaluated using Spearman’s rho. Results: The percentage of babies born small-for-gestational-age reduced by 0.3% across the evaluation period. Antenatal small-for-gestational-age diagnosis rose from 4.1% to 14.3%. However, the number of false-positive cases of antenatally diagnosed small-for-gestational-age increased fivefold from 2.2% to 11.5%. Although stillbirth rates remained consistent post-Growth Assessment Protocol, complex scan volume (e.g. number of growth scans using Doppler) increased annually. The peak incline coincided with the Growth Assessment Protocol implementation period (2016–2018). Complex scan volume was significantly associated with overall small-for-gestational-age detection (rho = 0.8, p =< 0.001), but not with stillbirth frequency (rho = −0.1, p = 0.4). Conclusion: Small-for-gestational-age detection increased following Growth Assessment Protocol implementation, although this was associated with a high false-positive rate and no reduction in stillbirths. The potential implications associated with clinical management, parent experiences and departmental workflow, alongside the benefits for stillbirth reduction, should be fully considered prior to the introduction of a new fetal growth initiative to the antenatal care pathway.

Support of the luteal phase in programs for transferring thawed embryos into the uterine cavity in patients with overweight and obesity

Introduction. Progesterone levels are a critical factor for embryo implantation in in vitro fertilization (IVF) programs, including thawed embryo transfer programs. Overweight/obese patients often have lower blood progesterone concentrations in the luteal phase during IVF cycles, which requires an individual approach to planning luteal support in this category of patients.Aim. To compare the pregnancy ratе and miscarriage rates up to 12 weeks of pregnancy in overweight/obese patients who underwent a program of transfer of thawed embryos into the uterine cavity, depending on the type and route of administration of gestagens.Materials and methods. The study included 76 overweight or obese patients. All patients were treated for infertility using a program for transferring a thawed embryo into the uterine cavity; luteal phase support was carried out either using micronized progesterone, identical to natural, – the drug Utrogestan in a daily dose of 800 mg intravaginally (40 patients), or combination therapy was prescribed – vaginal gel with progesterone 90 mg in combination with the synthetic progestin dydrogesterone in a daily dose of 30 mg, taken orally (36 patients).Results. The rates of pregnancy and miscarriage in the first trimester were comparable in both groups and did not depend on differences in luteal support.Conclusions. The formation of the luteal phase of the cycle in patients with overweight/obesity is equally effective using various forms of gestagens. The use of micronized progesterone may be preferable in patients with overweight/obesity in terms of the ability to monitor blood progesterone levels, a more favorable metabolic profile when used vaginally, and the possibility of switching to oral administration of the drug in the event of the development of adverse local events.

Comparative study on pregnancy complications: PGT-A vs. IVF-ET with gender-specific outcomes

The safety and clinical effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) in improving pregnancy outcomes for sub-fertile patients remains controversial. Potential sex-based differences in the relationship between PGT-A and pregnancy complications have not been investigated, which could guide the appropriate clinical application of PGT-A. In this secondary analysis of data from a multicenter, randomized, controlled, non-inferiority trial (NCT03118141), 940 women who achieved singleton live birth during the trial were included to estimate the between-group differences in pregnancy complications following PGT-A versus conventional in vitro fertilization (IVF) vary with fetal sex. Logistic regression analysis was used to adjust for possible confounders, and subgroup analysis was also performed. Among male fetuses, the risk of maternal preeclampsia was significantly lower after PGT-A compared to conventional IVF treatment (3.37% vs. 7.88%; adjusted OR, 0.40; 95% CI, 0.17-0.92; P = 0.032). However, this protective effect was not observed in pregnancies with female fetuses (3.63% vs. 3.38%; adjusted OR, 1.04; 95% CI, 0.36-3.00; P = 0.937). In addition, no significant sex-dependent differences in the risks of other pregnancy complications or neonatal outcomes were detected between PGT-A and conventional IVF groups (P > 0.05). In summary, PGT-A was associated with a decreased risk of maternal preeclampsia in singleton pregnancies with male fetuses, highlighting its potential utility in preeclampsia prevention in addition to spontaneous abortion rate reduction.

Recipients' age, fresh embryo and blastocyst-stage embryo transfer as favorable factors in a transnational oocyte donation program.

In Italy, egg donation is being allowed again following the ruling by the Constitutional Court N. 162/2014. Nevertheless, the number of voluntary donors is insignificant, probably because no reimbursement is provided. Therefore, the great majority of egg donation cycles are performed by using imported cryopreserved oocytes from foreign countries. However, recent evidence has questioned the overall efficacy of this strategy in comparison with the shipment of frozen sperm and vitrified embryos. Retrospective cohort study, conducted at ANDROS Day Surgery Clinic Palermo, Italy in the period 2016-2022, with the objective of evaluating the efficiency of each batch of vitrified oocytes, in terms of completed cycles. The cryopreserved donated oocytes came from a single Spanish clinic (Next Fertility, Valencia, Spain). The primary outcome was the cumulative live birth rate (CLBR). The secondary outcomes were the cumulative ongoing pregnancy rate (COPR), the cumulative clinical pregnancy rate (CCPR) and the miscarriage rate. The CLBR totaled 35.1%, the COPR 36.8%, the CCPR 49.2% and the miscarriage rate 24.7%. In the multivariate analysis, the probability of success was significantly higher in younger recipients, in fresh embryo transfer and in blastocyst-stage embryo transfer. Our "transnational" donation program with vitrified oocytes has good success rates. The main focus of our analysis is the negative effect of advancing recipient age on success rates, outlining a possible, important role of age-related uterine factor on implantation mechanisms. This aspect should be emphasized during the counselling with couples much more than is routinely done.

Triggering oocyte maturation in IVF treatment in normal responders: a systematic review and network meta-analysis.

To compare efficacy and safety of hCG, GnRH agonist, dual, and double triggers in predicted normal responders undergoing ovarian stimulation and IVF DESIGN: A systematic review and network meta-analysis of randomized controlled trials (RCTs). RCTs indexed in PubMed, MEDLINE, EMBASE, clinical trial registries and Cochrane Database of Systematic Reviews up to December 2023. Twelve high-integrity RCTs comprising 1,931 women were included, which compared hCG trigger to GnRH agonist trigger, dual trigger, and double trigger. Statistical analysis was performed using STATA version 16. Key outcomes included clinical pregnancy rates (CPR), live birth rates (LBR), number of oocytes, number of mature oocytes, miscarriage rate and rates of ovarian hyperstimulation syndrome (OHSS). The network meta-analysis for CPR were relative risk (RR) 1.13 (95% Confidence Interval (CI):0.80-1.60) for hCG versus GnRH agonist trigger, RR 1.23 (95% CI:0.92-1.65) for hCG versus dual trigger, RR 0.38 (95% CI:0.21-0.69) for hCG versus double trigger, RR 1.09 (95% CI:0.70-1.70) for GnRH agonist versus dual trigger and 0.34 (95% CI:0.17-0.67) for GnRH agonist versus double trigger and RR 0.31 (95%CI:0.16-0.60) for double versus dual trigger. Dual trigger demonstrated the highest SUCRA (85.1%), indicating superior efficacy for clinical pregnancy rates. For LBR, while connectivity was limited, the RR was 1.31 (95% CI: 1.00-1.70) for dual versus hCG trigger, and RR 1.60 (95% CI: 1.05-2.43) for dual versus GnRH agonist trigger. OHSS rates were significantly lower with the GnRH agonist compared to hCG trigger (RR 0.56, 95% CI: 0.19-1.75). There were no randomized controlled trials reporting OHSS rates with the use of dual or double trigger. No significant differences were observed in the number of oocytes retrieved, mature oocytes, or miscarriage rates among the trigger protocols. The findings indicate that there is no evidence to suggest that using GnRH agonist, dual, or double protocols is superior to hCG trigger in improving clinical pregnancy rates. While live birth rates may benefit from dual trigger, results are limited by available RCTs. Larger, multicentre trials are needed for further evaluation of live birth rates and understanding of long-term outcomes.

Analysis of Pregnancy Outcomes in Patients Exhibiting Recurrent Miscarriage With Concurrent Low-Titer Antiphospholipid Antibodies.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and adverse pregnancy outcomes, often associated with elevated antiphospholipid antibodies (aPLs). The 2023 ACR/EULAR criteria for APS necessitate persistent medium to high titers of aPLs for laboratory confirmation. However, the impact of persistently low-titer aPLs in recurrent miscarriage (RM) patients remains controversial. This study aims to analyze the effect of treatment on pregnancy outcomes and maternal-fetal complications in patients with low-titer aPLs. The study encompassed 252 pregnancies in 237 RM patients tested for aPLs at the Third Hospital of Guangzhou Medical University from January 2018 to July 2022. Patients were divided into two groups based on aPLs titers: 86 with low-titer aPLs (92 pregnancies) and 151 aPLs-negative (160 pregnancies). Of the low-titer group, 71 received treatment, while 21 and all aPLs-negative patients did not. Seventy-one treated patients with low-titer aPLs were divided into two groups. Group A (n = 15) received a standard treatment regimen that included low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH). In contrast, Group B (n = 56) received a multidrug regimen, which included hydroxychloroquine (HCQ) and/or glucocorticoids (GC) and/or intravenous immunoglobulin (IVIG) in addition to the standard treatment of LDA and LMWH. Pregnancy outcomes and maternal-fetal complications were subsequently compared. The highest positivity rates were for aCL-IgM (76.2% in the untreated low-titer aPLs group and 81.7% in the treated low-titer aPLs group), followed by aβ2GPI-IgM (23.8% in the untreated low-titer aPL group and 11.4% in the treated low-titer aPLs group), and LA (5.6% in the untreated low-titer aPLs group and 3.3% in the treated low-titer aPLs group). Single antibody positivity was 90.5% in the untreated low-titer aPL group and 87.3% in the treated low-titer aPLs group, with double positivity at 9.5% in the untreated low-titer aPLs group and 12.7% in the treated low-titer aPLs group. No triple positivity was detected. The treated low-titer aPLs group had more previous miscarriages (p < 0.05) and a higher ANA positivity rate (p < 0.05) than the aPLs-negative group. Additionally, the treated low-titer aPLs group had lower complement levels than the aPLs-negative group. Immunoglobulin IgM levels were higher in both the untreated and treated low-titer aPL groups compared to the aPLs-negative group (p < 0.05). Post treatment, the live birth rate in the low-titer group significantly exceeded that of the untreated group (67.6%vs. 33.3%; p = 0.005). The miscarriage rate was notably lower in untreated low-titer patients compared to aPLs-negative patients (32.4%vs. 66.7%; p = 0.005). No significant differences were observed in maternal or fetal complications between the groups. In the standard treatment group (Group A), there were 8 (53.3%) live births, whereas the multidrug treatment group (Group B) had 40 (71.4%) live births, a significantly higher rate than in the standard treatment group, although the difference lacked statistical significance. The study indicates that untreated RM patients with low-titer positive aPLs have a higher recurrence of miscarriage compared to the aPLs-negative RM group. However, recurrence significantly decreases following appropriate intervention, suggesting the benefits of treatment for RM patients with low-titer aPLs.

Global, regional, and national stillbirths at 20 weeks' gestation or longer in 204 countries and territories, 1990–2021: findings from the Global Burden of Disease Study 2021

Stillbirth is a devastating and often avoidable adverse pregnancy outcome. Monitoring stillbirth levels and trends-in a comprehensive manner that leaves no one uncounted-is imperative for continuing progress in pregnancy loss reduction. This analysis, completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, methodically accounted for different stillbirth definitions with the aim of comprehensively estimating all stillbirths at 20 weeks or longer for 204 countries and territories from 1990 to 2021. We extracted data on stillbirths from 11 412 sources across 185 of 204 countries and territories, including 234 surveys, 231 published studies, 1633 vital statistics reports, and 10 585 unique location-year combinations from vital registration systems. Our final dataset comprised 11 different definitions, which were adjusted to match two gestational age thresholds: 20 weeks or longer (reference) and 28 weeks or longer (for comparisons). We modelled the ratio of stillbirth rate to neonatal mortality rate with spatiotemporal Gaussian process regression for each location and year, and then used final GBD 2021 assessments of fertility and all-cause neonatal mortality to calculate total stillbirths. Secondary analyses evaluated the number of stillbirths missed with the more restrictive gestational age definition, trends in stillbirths as a function of Socio-demographic Index, and progress in reducing stillbirths relative to neonatal deaths. In 2021, the global stillbirth rate was 23·0 (95% uncertainty interval [UI] 19·7-27·2) per 1000 births (stillbirths plus livebirths) at 20 weeks' gestation or longer, compared to 16·1 (13·9-19·0) per 1000 births at 28 weeks' gestation or longer. The global neonatal mortality rate in 2021 was 17·1 (14·8-19·9) per 1000 livebirths, corresponding to 2·19 million (1·90-2·55) neonatal deaths. The estimated number of stillbirths occurring at 20 weeks' gestation or longer decreased from 5·08 million (95% UI 4·07-6·35) in 1990 to 3·04 million (2·61-3·62) in 2021, corresponding to a 39·8% (31·8-48·0) reduction, which lagged behind a global improvement in neonatal deaths of 45·6% (36·3-53·1) for the same period (down from 4·03 million [3·86-4·22] neonatal deaths in 1990). Stillbirths in south Asia and sub-Saharan Africa comprised 77·4% (2·35 million of 3·04 million) of the global total, an increase from 60·3% (3·07 million of 5·08 million) in 1990. In 2021, 0·926 million (0·792-1·10) stillbirths, corresponding to 30·5% of the global total (3·04 million), occurred between 20 weeks' gestation and 28 weeks' gestation, with substantial variation at the country level. Despite the gradual global decline in stillbirths between 1990 and 2021, the overall number of stillbirths remains substantially high. Counting all stillbirths is paramount to progress, as nearly a third-close to 1 million in total-are left uncounted at the 28 weeks or longer threshold. Our findings draw attention to the differential progress in reducing stillbirths, with a high burden concentrated in countries with low development status. Scarce data availability and poor data quality constrain our capacity to precisely account for stillbirths in many locations. Addressing inequities in universal maternal health coverage, strengthening the quality of maternal health care, and improving the robustness of data systems are urgently needed to reduce the global burden of stillbirths. Bill & Melinda Gates Foundation.

Reproductive and pregnancy control in Wilson disease patients in Spain.

Recommendations on pregnancy, lactation, and contraception in women with Wilson disease are briefly stated in international guidelines but are not entirely homogeneous. Data regarding the management of these special events among patients with Wilson disease in Spain are lacking. We used the Wilson Registry platform of the Spanish Association for the Study of the Liver to question patients on their reproductive and gestational lives. This was a multicentre ambispective study including adult women with Wilson disease in the Spanish Wilson Registry interviewed about their contraception, childbearing, pregnancy, and lactation experiences. Clinical and analytical data were extracted from the registry. The study included 92 women from 17 centres in Spain. Most (63%) reported having a previous pregnancy history. The rate of spontaneous miscarriages was 21.6%, mainly occurring in the first trimester and up to one third among undiagnosed patients. Most pregnant women received chelator therapy during pregnancy, but dose reduction was recommended in less than 10%. After delivery, artificial lactation predominated (60.3%) and its use was mainly based on physician's recommendations (68%). Up to 40% of the women included reported some concerns about their reproductive lives, mainly related to the potential drug toxicity to their children. Most of the patients considered the information given by specialists to be sufficient. Gestational management among women with Wilson disease in Spain was found to be highly heterogeneous and frequently different from what is described in international guidelines. Education on rare liver diseases should be a priority for scientific societies in order to homogenize patient follow-up and recommendations.

A comparative study on the clinical efficacy and pregnancy outcomes of methimazole and propylthiouracil in managing pregnancy complicated with hyperthyroidism

The objective of the study was to compare the clinical efficacy and pregnancy outcomes of methimazole and propylthiouracil in managing hyperthyroidism during pregnancy. This retrospective analysis included 100 pregnant women with hyperthyroidism, who were divided into two groups: the methimazole group (Group A) and the propylthiouracil group (Group B). Indicators such as thyroid function, liver function, pregnancy outcomes, and newborn health were closely monitored. The results revealed that both groups experienced a reduction in thyroid function indicators, with Group B showing a more modest decrease. Group B exhibited a higher incidence of liver injury but also achieved more full-term pregnancies. There were no significant differences in adverse reactions, miscarriage rates, or cesarean rates between the two groups. Apgar scores were higher in Group B, while neonatal weights were comparable. We conclude that propylthiouracil improved thyroid function more substantially than methimazole although it was associated with a higher risk of liver injury.

Laparotomy versus laparoscopy for the treatment of adnexal torsion during pregnancy

BackgroundAdnexal torsion (AT) is a rare emergency complication during pregnancy. Increasing evidence implies that operative laparoscopy for adnexal torsion performed during pregnancy could be safe and feasible. We procured and evaluated the surgical and obstetric outcomes between laparoscopy and laparotomy to determine the optimal approach for treating AT during pregnancy.MethodsThis was a retrospective study involving telephone questionnaire on adnexal torsion during pregnancy that occurred between July 2012 and July 2023 in the First Affiliated Hospital of Zhengzhou University. The study cohort included 155 pregnant women who underwent laparotomy or laparoscopic surgery. The clinical characteristics, surgical interventions, postoperative pathology and pregnancy outcomes were analyzed.ResultsA total of 102 patients were treated by laparoscopy, and 53 patients were treated by laparotomy. Compared with the laparotomy group, the laparoscopy group had significantly less blood loss (17.5 ml vs. 20.0 ml, p = .004), a lower incidence of delayed incision healing (1.0% vs. 11.3%, p = .011), and a shorter hospital stay (5.0 days vs. 8.0 days, p < .001). There was no significant difference between the two groups in terms of obstetric outcomes, including preterm delivery, miscarriage rate, birth weight, delivery gestation, cesarean delivery rate, or neonatal intensive care unit admission. All the pathological findings were benign except for one case of borderline mucinous cystadenoma. The most common pathological types were luteal cysts in the laparoscopy group and mature teratomas in the laparotomy group.ConclusionIn this retrospective study, compared with laparotomy, laparoscopy yielded successful outcomes, with less surgical bleeding, less delayed wound healing, and shorter hospital stays. Laparoscopy could be a promising approach for diagnosing and treating AT during pregnancy.

Intrauterine infusion of autologous platelet rich plasma can be an efficient treatment for patients with unexplained recurrent implantation failure

The studies posits that there is not sufficient evidence to support the use of intrauterine platelet-rich plasma (PRP) infusion in patients with recurrent implantation failure (RIF). This study aims to investigate the effects of infusion of PRP on patients with unexplained-RIF in fresh and frozen embryo transfer (ET) cycles. A total of 80 participants were included in this study. The participants were randomly assigned to one of two groups with and without PRP infusion. Each of the PRP and control groups were also divided into fresh and frozen ET subgroups. ET outcomes were compared between groups. Clinical pregnancy rate was significantly higher in Frozen ET in PRP group than other subgroups (p < 0.0001). Miscarriage rate were significantly lower in PRP group than control group. Pregnancy complications and preterm labor were significantly higher in PRP group than control group (p < 0.0001). Live birth and healthy baby rate were significantly higher in PRP group than control group (p < 0.0001). The intrauterine infusion of 0.8-1 ml of PRP 48 h before blastocyst ET at fresh and frozen cycles can be an efficient treatment option for u-RIF patients. Also, results indicated that the clinical pregnancy rate was equal to the live birth rate at fresh ET cycles, whereas the live birth rate was lower than the clinical pregnancy rate at frozen ET cycles. Therefore, considering the superiority of fresh cycles over freeze cycles, the infusion of PRP into the uterus of patients with RIF is recommended to be done at fresh ET cycles.Trial registration: NCT, NCT03996837. Registered 25/06/2019. Retrospectively registered, http://www.clinicaltrial.gov/ NCT03996837.

Inequity in Fertility Treatment for Patients that Speak a Language Other than English: A Retrospective Cohort Study.

To assess fertility treatment outcomes according to primary language spoken in patients undergoing fertility treatment in an Australian setting. This retrospective cohort study examined female patients who received fertility treatment through a public hospital fertility service between September 2020 and May 2023. The primary outcome was clinical pregnancy rate following embryo transfer for patients who spoke English and patients who primarily spoke a language other than English. Poisson regression was used to estimate the association between language spoken and clinical pregnancy rate. Secondary outcomes included rate of other pregnancy outcomes following embryo transfer, number of fertility treatments performed, embryo quality, IVF cancellation rate, discontinuation rate, and time from first fertility appointment to treatment commencement. Of the 916 patients who accessed fertility treatment during the study period, 112 patients (12.23%) primarily spoke a language other than English. There were no significant differences in clinical pregnancy rate following embryo transfer (IRR 0.92, 95% CI 0.60-1.36), or rates of biochemical pregnancy, miscarriage, or negative pregnancy. However, patients who spoke a language other than English received significantly fewer IVF cycles (1.29 ± 0.61 vs 1.63 ± 1.16 cycles, p = 0.006), greater all-cause IVF cancellation rate (41.33% vs 28.33%, p = 0.048), and longer median time from first appointment to first treatment of any type (341 vs 234.5days, p < 0.001). Inequity in all-cause IVF cancellation rate, mean number of IVF cycles, and duration from first fertility appointment to treatment commencement were observed for patients who spoke a language other than English.

The effect of sequential embryo transfer on pregnancy outcomes in patients with recurrent implantation failure: a systematic review and meta-analysis of randomized controlled trials.

The aim of our study was to assess the impact of sequential embryo transfer on pregnancy outcomes among patients with recurrent implantation failure (RIF). We conducted a comprehensive search across various databases for eligible clinical trials from inception to January 2024. Randomized controlled trials (RCTs) were included if they compared sequential embryo transfer, comprising both cleavage-stage and blastocyst-stage embryos, with other transfer protocols in infertile women with repeated implantation failure. Meta-analysis was performed using Revman software. Our primary focus was on the ongoing pregnancy rate. Our secondary measures included rates of chemical pregnancies, clinical pregnancies, miscarriages, and multiple pregnancies. Seven RCTs, encompassing 909 patients, met the inclusion criteria. Sequential embryo transfer demonstrated a significant increase in the ongoing pregnancy rate compared to the control group (OR = 2.28, 95% CI [1.46, 3.56], p = 0.003). Moreover, the sequential embryo transfer group exhibited notable improvements in chemical and clinical pregnancy rates. There were no statistically significant differences between the groups regarding multiple pregnancy and miscarriage rates (p > 0.05). Sequential embryo transfer shows promise in enhancing pregnancy outcomes among RIF patients. However, additional trials are warranted to validate our findings.