Improving Miscarriage Prevention Research: a survey exploring the expectations of service users and stakeholders (IMPRESS) - a study protocol for a UK-based survey.

INTRODUCTION: Interventional clinical trials in recurrent miscarriage use varying expected effect sizes to inform their sample size calculations. Often these are not informed by what stakeholders consider a meaningful treatment effect. Adaptive trial designs may integrate stakeholder views on trial success and futility but the criteria to inform this is lacking. This study aims to understand relevant stakeholder views of what is considered a worthwhile treatment effect for miscarriage prevention interventions and what is acceptable stopping criteria in miscarriage clinical trials. METHODS AND ANALYSIS: The study is designed as a cross-sectional online anonymous survey. The survey presents different scenarios to respondents relating to varying target differences and probability thresholds and explores success and futility criteria for clinical trials. The survey was developed with personal and public involvement (PPI) through focus groups and a PPI partner. Eligible participants will be those with a personal history of miscarriage, including partners, and healthcare professionals who manage patients who experience a miscarriage. Convenience, snowball and purposive sampling techniques will be employed to invite eligible participants to complete the survey. The survey will be accepting responses for an initial 2-week pilot to check validity, prior to being open for a further 12 weeks. Descriptive analyses and linear regression analyses will synthesise the survey results. ETHICS AND DISSEMINATION: Ethical approval was obtained from the NHS Research Ethics Committee North West-Greater Manchester East (23/NW/0322) on 30 January 2024. Informed consent will be obtained prior to survey completion. No personal identifying information will be collected. The results will be published in a relevant scientific journal and communicated through our institutional website.

Improvement of early miscarriage rates in women with adenomyosis via oxytocin receptor antagonist during frozen embryo transfer-a propensity score-matched study.

BACKGROUND: Dysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis. METHODS: Between January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses. RESULTS: The study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis. CONCLUSIONS: Administering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.

Effect of estrogen exposure on pregnancy outcomes in artificial frozen-thawed embryo transfer cycles.

In contemporary times, the employment of vitrification freezing technology has led to the widespread adoption of frozen-thawed embryo transfer (FET) worldwide. Meanwhile, hormone replacement therapy (HRT) is a crucial protocol for priming the endometrium during FET cycles. Estrogen is required in HRT cycles for the induction of progesterone receptors and to promote endometrial thickness. However, there is no universal consensus on the treatment duration, dosage regimen, administration route, and target serum estrogen levels. Therefore, this study aimed to offer a comprehensive review of these topics. A shorter duration of estrogen exposure may elevate the risk of early miscarriage, while prolonged exposure to estrogen does not seem to confer advantages to general population and may be attempted in individuals with thin endometrium. Moreover, excessive estrogen levels on the day of progesterone administration may be associated with higher miscarriage rates and lower live birth rates (LBR). To offer more comprehensive guidance for clinical practice, extensive and prospective studies involving a large sample size are warranted to determine the optimal concentration and duration of estrogen exposure.

Analysis of perinatal outcomes for emergency cervical cerclage in singleton pregnancies at 24-28 weeks of gestation.

BACKGROUND: Cervical cerclage is the only effective treatment for cervical insufficiency, effectively preventing late miscarriage and preterm birth. The effectiveness and safety of emergency cervical cerclage (ECC) as an emergency treatment when the cervix is already dilated or when there is protrusion of the fetal membranes into the vagina remain controversial, especially in pregnancies at 24-28 weeks when the fetus is viable. There is still no consensus on whether emergency cervical cerclage should be performed in such cases. PURPOSE: To investigate the effectiveness and safety of emergency cervical cerclage in singleton pregnant women at 24-28 weeks of gestation. METHODS: This study employed a single-center prospective cohort design, enrolling singleton pregnant women at 24-28 weeks of gestation with ultrasound or physical examination indicating cervical dilation or even membrane protrusion. Emergency cervical cerclage was compared with conservative treatment. The primary endpoints included a comprehensive assessment of perinatal pregnancy loss, significant neonatal morbidity, and adverse neonatal outcomes. Secondary endpoints included prolonged gestational age, preterm birth, neonatal hospitalization rate, premature rupture of membranes, and intrauterine infection/chorioamnionitis. RESULTS: From June 2021 to March 2023, a total of 133 pregnant women participated in this study, with 125 completing the trial, and were allocated to either the Emergency Cervical Cerclage (ECC) group (72 cases) or the conservative treatment group (53 cases) based on informed consent from the pregnant women. The rate of adverse neonatal outcomes was 8.33% in the ECC group and 26.42% in the conservative treatment (CT) group, with a statistically significant difference (P = 0.06). There were no significant differences between the two groups in terms of perinatal pregnancy loss and significant neonatal morbidity. The conservative treatment group had a mean prolonged gestational age of 63.0 (23.0, 79.5) days, while the ECC group had 84.0 (72.5, 89.0) days, with a statistically significant difference between the two groups (P < 0.001). Compared with CT group, the ECC group showed a significantly reduced incidence of preterm birth before 28 weeks, 32 weeks, and 34 weeks, with statistical significance (P = 0.046, 0.007, 0.001), as well as a significantly decreased neonatal hospitalization rate (P = 0.013, 0.031). Additionally, ECC treatment did not increase the risk of preterm premature rupture of membranes or intrauterine infection/chorioamnionitis, with no statistically significant differences (P = 0.406, 0.397). CONCLUSION: In singleton pregnant women with cervical insufficiency at 24-28 weeks of gestation, emergency cervical cerclage can reduce adverse neonatal pregnancy outcomes, effectively prolong gestational age, decrease preterm births before 28 weeks, 32 weeks, and 34 weeks, lower neonatal hospitalization rates, and does not increase the risk of preterm premature rupture of membranes or intrauterine infection/chorioamnionitis.

Perinatal outcomes between immediate vs deferred selective termination in dichorionic twin pregnancies with fetal congenital anomalies: a French multicenter study.

BACKGROUND: Because selective termination for discordant dichorionic twin anomalies carries a risk of pregnancy loss, deferring the procedure until the third trimester can be considered in settings where it is legal. OBJECTIVE: To determine whether perinatal outcomes were more favorable following deferred rather than immediate selective termination. STUDY DESIGN: A French multicenter retrospective study from 2012 to 2023 on dichorionic twin pregnancies with selective termination for fetal conditions, which were diagnosed before 24 weeks gestation. Pregnancies with additional risk factors for late miscarriage were excluded. We defined 2 groups according to the intention to perform selective termination within 2 weeks after the diagnosis of the severe fetal anomaly was established (immediate selective termination) or to wait until the third trimester (deferred selective termination). The primary outcome was perinatal survival at 28 days of life. Secondary outcomes were pregnancy losses before 24 weeks gestation and preterm delivery. RESULTS: Of 390 pregnancies, 258 were in the immediate selective termination group and 132 in the deferred selective termination group. Baseline characteristics were similar in both groups. Overall survival of the healthy co-twin was 93.8% (242/258) in the immediate selective termination group vs 100% (132/132) in the deferred selective termination group (P<.01). Preterm birth <37 weeks gestation was lower in the immediate than in the deferred selective termination group (66.7% vs 20.2%; P<.01); preterm birth <28 weeks gestation and <32 weeks gestation did not differ significantly (respectively 1.7% vs 0.8%; P=.66 and 8.26% vs 11.4%; P=.36). In the deferred selective termination group, an emergency procedure was performed in 11.3% (15/132) because of threatened preterm labor, of which 3.7% (5/132) for imminent delivery. CONCLUSION: Overall survival after selective termination was high regardless of the gestational age at which the procedure was performed. Postponing selective termination until the third trimester seems to improve survival, whereas immediate selective termination reduces the risk of preterm delivery. Furthermore, deferred selective termination requires an expert center capable of performing the selective termination procedure on an emergency basis if required.

Oral dydrogesterone for prevention of miscarriage in threatened miscarriage: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine the effectiveness of oral dydrogesterone in preventing miscarriage in threatened miscarriage. METHODS: A randomized, controlled trial study was conducted among pregnant Thai women at the gestational age of six to less than 20 weeks who visited King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand with threatened miscarriage from August 2021 to August 2022. These pregnant women were randomized to receive oral dydrogesterone 20 mg per day or placebo twice a day until one week after vaginal bleeding stopped or otherwise for a maximum of six weeks. RESULTS: A total of 100 pregnancies were recruited. Fifty of them were assigned to receive oral dydrogesterone and 50 were assigned to receive placebo. The rate of continuing pregnancy beyond 20 weeks of gestational age was 90.0% (45 out of 50 women) in the dydrogesterone group and 86.0% (43 out of 50 women) in the placebo group (p = 0.538). The incidence of adverse events did not differ significantly between the groups. CONCLUSION: Oral dydrogesterone 20 mg/day could not prevent miscarriages in women with threatened miscarriage.

Effectiveness of metformin to pregnant women with PCOS to reduce spontaneous abortion and gestational diabetes mellitus: a protocol for an overview of reviews.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a globally prevalent endocrinological disorder and has been associated with poor pregnancy outcomes, including a higher rate of gestational diabetes and miscarriage. Metformin is among the drugs investigated to improve the prognosis of pregnant women with PCOS. OBJECTIVE: To conduct an overview of systematic reviews examining the effects of metformin versus placebo or no intervention throughout pregnancy among pregnant women with a preconception PCOS diagnosis to reduce the incidence of miscarriage and gestational diabetes. METHODS AND ANALYSIS: We will perform an overview of systematic reviews by searching Embase, PubMed, Virtual Health Library, Cochrane Central Register of Controlled Trials, Trip Database, Scopus, Web of Science and Cumulative Index to Nursing and Allied Health Literature from inception to 17 August 2023. Language, publication status and year indexed or published filters will not be applied. Two reviewers will independently screen and select papers, assess their quality, evaluate their risk of bias and collect the data. The included reviews will be summarised narratively. The quality and risk of bias of the systematic review and meta-analysis studies included will be assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews, Second Version) and ROBIS (Risk of Bias in Systematic Reviews), respectively. ETHICS AND DISSEMINATION: This overview of reviews will analyse data from systematic reviews on the use of metformin for prepregnancy diagnosis of PCOS to reduce adverse outcomes. As there will be no primary data collection, a formal ethical analysis is unnecessary. The study outcomes will be submitted to a peer-reviewed journal and presented at conferences. PROSPERO REGISTRATION NUMBER: CRD42023441488.

Progesterone in Pregnancy: Evidence-Based Strategies to Reduce Miscarriage and Enhance Assisted Reproductive Technology.

The incidence of miscarriage in early pregnancy, between 5-20 weeks, is common, with a prevalence of between 5-22% of all pregnancies. Miscarriage can have physical, social, and mental health impacts on women and their families. In societies such as Taiwan, where the birth rate is falling and life expectancy is increasing, there is concern that factors that reduce birth rates will have detrimental economic and societal effects. Progesterone has a significant role in maintaining early and successful pregnancy to term. Evidence from preclinical and clinical research on the roles of progesterone has supported recent clinical guidelines in obstetrics and gynecology to reduce rates of early miscarriage and improve methods of assisted reproductive technology (ART). This article aims to present an evidence-based review of current recommendations for the use of progesterone in early pregnancy to reduce miscarriage rates and in luteal phase support for ART, including embryo transfer.

A rapid improvement event: progesterone prescribing in prevention of miscarriage.

A rapid improvement event (RIE) is a standard operational excellence technique that uses team-based problem solving to improve processes. In this study, a RIE was undertaken to improve progesterone prescribing rates for those with a history of miscarriage experiencing vaginal bleeding in early pregnancy. This was on the basis of a recent change in guidelines regarding prescribing in these instances. NICE guidelines changed in November 2021 after Cochrane meta-analysis and the PRISM (Progesterone in Spontaneous Miscarriage) randomised control trial demonstrated a higher incidence of live births in those prescribed vaginal micronised progesterone for threatened miscarriage, when compared with those not prescribed it.A RIE involves a team approach and a standard sequence of events allowing analysis and improvement of a process. Analysis in the form of audit revealed a low progesterone prescribing rate for eligible patients in our unit. Dissection of this problem into its elements revealed a low level of staff knowledge regarding the change in guidelines and a lack of confidence in prescription of progesterone. A plan of actionable events to improve prescribing rates was devised. The updated guidance and local recommendations on appropriate micronised progesterone formulations were presented at hospital Grand Rounds with multidisciplinary attendance. Infographics were displayed in areas visible to stakeholders within the hospital and on the hospital's social media pages. The validity of these educational measures to improve the process was reaudited after 3 months.Progesterone prescribing improved by 48%. Those comfortable with prescribing as per the new guidelines improved from 43% to 78%. A RIE proved to be an effective and efficient approach to collaboration, decision-making and action.

[Prevention of Rh D alloimmunization in the first trimester of the pregnancy: French College of Obstetricians and Gynecologists guidelines for clinical practice]. / Prévention de l'allo-immunisation anti-RH1 au premier trimestre de la grossesse : recommandations pour la pratique clinique du Collège national des gynécologues-obstétriciens français.

OBJECTIVE: To provide recommendations for the prevention of Rh D alloimmunization in the first trimester of pregnancy. MATERIALS AND METHODS: The quality of evidence of the literature was assessed following the GRADE methodology with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on Pubmed, Cochrane, EMBASE, and Google Scholar databases. The quality of evidence was assessed (high, moderate, low, very low) and a recommendation was formulated: (i) strong, (ii) weak, or (iii) no recommendation. The recommendations were reviewed in two rounds with reviewers from the scientific board of the French College of the OB/GYN (Delphi survey) to select the consensus recommendations. RESULTS: The three recommendations from PICO questions reached agreement using the Delphi method. It is recommended not to administer Rh D immunoglobulin before 12 weeks of gestation to reduce the risk of alloimmunization in case of abortion or miscarriage, in RhD negative patients when the genitor is RhD positive or unknown (Weak recommendation. Very low-quality evidence). It is recommended not to administer Rh D immunoglobulin before 12 weeks of gestation to reduce the risk of alloimmunization in cases of bleeding in an ongoing intrauterine pregnancy (Weak recommendation. Very low-quality evidence). The literature data are insufficient in quality and quantity to determine if the injection of Rh D immunoglobulin reduces the risk of alloimmunization in the case of an ectopic pregnancy (No recommendation. Very low-quality evidence). CONCLUSION: Even though the quality of evidence from the studies is very low, it is recommended not to administer Rh D immunoglobulin in case of abortion, miscarriage or bleeding before 12 weeks of amenorrhea. The quality of evidence was too low to issue a recommendation regarding ectopic pregnancy.

Jianpi Antai formula prevents miscarriage by repressing M1 polarization of decidual macrophages through ubiquitination of NLRP3 mediated by MARCH7.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianpi Antai Formula (JAF) is an ancient formula from He's gynecology, which has been used clinically for more than 30 years and has significant therapeutic effects on spontaneous abortion (SA). Both macrophage polarization and NLRP3 inflammasome correlate with the occurrence of SA in women with recurrent or threatened miscarriage. Whether JAF prevent SA via mediating activation of decidual macrophage (dMφ) and ubiquitination-associated degradation of NLRP3 remains uncertain. AIM OF THE STUDY: This study aimed to clarify the effects of JAF on pregnancy outcomes and dMφ polarization at the maternal-fetal interface in an SA mouse model, and use in vivo and invitro methods to explore whether JAF can inhibit M1 polarization of dMφ by up-regulating MARCH7-mediated NLRP3 ubiquitination, thereby preventing SA. MATERIALS AND METHODS: The CBA/J × DBA/2 mating method was used to establish an SA model and the dMφs of SA mice were isolated and cultured. Th1-, Th2-, Th17- and Treg-related cytokine levels were evaluated using ELISA. qRT-PCR was used to detect the levels of M1/M2 macrophage-related cytokine mRNA in the decidua, and western blotting was used to detect the expression of NLRP3 inflammasome-related proteins in the decidua and placenta. The expression of M1/M2 markers of dMφ was detected using flow cytometry, ASC speck formation was observed using immunofluorescence, and the ubiquitination level of MARCH7-NLRP3 was detected using co-immunoprecipitation. RESULTS: JAF increased the survival rate of fetuses and the levels of estradiol and progesterone in SA model mice. It also reduced the serum Th1 and Th17-associated cytokine levels and decidual M1 macrophage-associated cytokine levels, while elevating the M2 macrophages in SA mice. NLRP3, caspase-1, ASC, and IL-1ß protein expression in the decidua and placenta were also reduced. si-MARCH7 transfection reversed the effect of JAF on inhibiting the formation of the NLRP3 inflammasome and the activation of macrophages in dMφs of SA mice. CONCLUSION: JAF could effectively prevent and treat SA by repressing M1 polarization of dMφs through NLRP3 ubiquitination and pyroptosis inhibition, which were mediated by MARCH7.

A randomized, controlled clinical study of low-molecular-weight heparin improving pregnancy outcomes in PCOS women undergoing IVF: study protocol.

BACKGROUND: Polycystic ovary syndrome (PCOS), an incidence of 10-15% in women of reproductive age, shows sex hormone disorders, luteal insufficiency, and the tendency of placental villus space thrombus. The incidence of early pregnancy loss in women with PCOS is three to eight times higher than that in non-PCOS women. PCOS women were reported in a pre-thrombotic state, which was manifested by accelerated thrombin production, increased PAI-1 activity, and fibrinogen. Other research also found an over-activated state of women with PCOS in immune system. Therefore, changing the prethrombotic state of PCOS through anticoagulation may be a new way to improve the adverse pregnancy outcome of PCOS. Low-molecular-weight heparin (LMWH) is the most common used anticoagulant drug in pregnancy, and it also was proposed for the prevention of recurrent abortion, although the application of LMWH in PCOS population during early pregnancy has not been reported. The objective of this study is to investigate the effect of LMWH on pregnancy outcomes after invitro fertilization-frozen embryo transfer (IVF-FET) in patients with polycystic ovary syndrome. METHODS: A total of 356 PCOS women aged between 20 and 38 years which prepared for IVF followed with FET will be enrolled in the study. The patients, from four different hospitals stratified by age and body mass index (BMI), will be randomly divided into the study group who will be treated with LMWH started on the day of progesterone transformation (hormone therapy) during FET cycle and the control group without additional medicine. Serum or urine hCG test will be given 14 days after embryo transfer to confirm biochemical pregnancy. If pregnancy is positive, LMWH+ hormone therapy/hormone therapy will be continued for another 2 weeks. Transvaginal ultrasonography will be performed 14 days later to confirm intrauterine pregnancy. The primary outcome is the ongoing pregnancy, which is defined as intrauterine live fetus with ultrasound after 12 weeks of gestation. DISCUSSION: This is the first study protocol to investigate the efficacy of LMWH as an adjuvant drug for IVF-FET outcomes in PCOS women, by comparing differences in ongoing pregnancy rate, clinical pregnancy rate, live birth rate, and early pregnancy loss rate between LMWH group and the control group. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2000036527. Registered on August 24, 2020.

A case-control retrospective study for the effect of Shoutai Wan on IVF-ET pregnancy outcome.

It has a long history of preventing and treating disease using traditional Chinese medicine (TCM). In recent years, it has been widely used in adjuvant therapies of in vitro fertilization - embryo transfer (IVF-ET) in China. To observe the effect and safety of Shoutai Wan on pregnancy outcomes after IVF-ET. A total of 352 patients who underwent IVF-ET from July 1, 2020 to June 30, 2021. The participants who only received routine luteal support during clinical pregnancy of FET were defined as the control group, and others who received TCM decoction Shoutai Wan for prevention of miscarriage and routine luteal support were defined as the Chinese medicine protection Shoutai Wan group (St group). This project has been approved by the Ethics Committee of Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine (Approval NO: 2023-0305). The results of this retrospective cohort study revealed that Shoutaiwan combined with luteal support treatment can significantly decreased the miscarriage rate in pregnancy undergoing IVF-FET compared to the group accepted only luteal support treatment (P = .001). Meanwhile, St during pregnancy did not affect fetal birth weight (P = .354), and there was no adverse event in the St group reported, which confirmed the safety of TCM for fetus protection during pregnancy. This study not only provides evidences for the clinical administration of Shoutai Wan in IVF-ET, but also provides a novel direction for basic research into the subsequent innovative application of TCM.

Cervical Cerclage: A Comprehensive Review of Major Guidelines.

Importance: Cervical cerclage (CC) represents one of the few effective measures currently available for the prevention of preterm delivery caused by cervical insufficiency, thus contributing in the reduction of neonatal morbidity and mortality rates. Objective: The aim of this study was to review and compare the most recently published major guidelines on the indications, contraindications, techniques, and timing of placing and removal of CC. Evidence Acquisition: A descriptive review of guidelines from the American College of Obstetricians and Gynecologists (ACOG), the Royal College of Obstetricians and Gynaecologists (RCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC), and the International Federation of Gynecology and Obstetrics (FIGO) on CC was carried out. Results: There is a consensus among the reviewed guidelines regarding the recommended techniques, the indications for rescue CC, the contraindications, as well as the optimal timing of CC placement and removal. All medical societies also agree that ultrasound-indicated CC is justified in women with history of prior spontaneous PTD or mid-trimester miscarriage and a short cervical length detected on ultrasound. In addition, after CC, serial sonographic measurement of the cervical length, bed rest, and routine use of antibiotics, tocolysis, and progesterone are unanimously discouraged. In case of established preterm labor, CC should be removed, according to ACOG, RCOG, and SOGC. Furthermore, RCOG and SOGC agree on the prerequisites that should be met before attempting CC. These 2 guidelines along with FIGO recommend history-indicated CC for women with 3 or more previous preterm deliveries and/or second trimester pregnancy miscarriages, whereas the ACOG suggests the use of CC in singleton pregnancies with 1 or more previous second trimester miscarriages related to painless cervical dilation or prior CC due to painless cervical dilation in the second trimester. The role of amniocentesis in ruling out intra-amniotic infection before rescue CC remains a matter of debate. Conclusions: Cervical cerclage is an obstetric intervention used to prevent miscarriage and preterm delivery in women considered as high-risk for these common pregnancy complications. The development of universal international practice protocols for the placement of CC seems of paramount importance and will hopefully improve the outcomes of such pregnancies.

Impact of Homocysteine as a Preconceptional Screening Factor for In Vitro Fertilization and Prevention of Miscarriage with Folic Acid Supplementation Following Frozen-Thawed Embryo Transfer: A Hospital-Based Retrospective Cohort Study.

Homocysteine is an amino acid naturally produced in the body and metabolized via the methionine cycle. High homocysteine levels can increase the risk of infertility and pregnancy complications, such as preeclampsia, preterm delivery, miscarriage, and low birth weight. Preconceptional homocysteine levels may be reduced by taking folic acid supplements to reduce the risk of such complications. This cross-sectional, hospital-based study was conducted to examine the role of homocysteine in 1060 infertile women with a history of IVF/intracytoplasmic sperm injection (ICSI) failure. We analyzed whether folic acid intervention altered homocysteine levels and influenced reproductive outcome. We found that a higher homocysteine level was statistically associated with a lower fertilization rate in patients with a history of IVF/ICSI failure. There was an inverse relationship between homocysteine levels and serum 25(OH)VD, and a trend towards lower anti mullerian hormone in the group with higher homocysteine levels. This is the first interventional study to identify that folic acid supplementation improved pregnancy outcomes following freeze embryo transfer (FET) in women with a history of FET failure by monitoring the reduction in homocysteine levels. Therefore, folic acid supplementation and homocysteine level monitoring may constitute a novel intervention for improving IVF/ICSI pregnancy outcomes.

Interventions to prevent miscarriage.

The physical and psychological impact of miscarriage can be devastating. There are many lifestyle and therapeutic interventions that may prevent a miscarriage. In this review, we have outlined the key areas for health optimization to prevent pregnancy loss, drawing on the most up-to-date evidence available. The 3 key areas identified are lifestyle optimization in women, lifestyle optimization in men, and therapeutic interventions. The evidence demonstrates that the treatments to consider are first-trimester progesterone administration, levothyroxine in women with subclinical hypothyroidism, and the combination of aspirin and heparin in women with antiphospholipid antibodies.

A core outcome set for trials in miscarriage management and prevention: An international consensus development study.

OBJECTIVE: To develop core outcome sets (COS) for miscarriage management and prevention. DESIGN: Modified Delphi survey combined with a consensus development meeting. SETTING: International. POPULATION: Stakeholder groups included healthcare providers, international experts, researchers, charities and couples with lived experience of miscarriage from 15 countries: 129 stakeholders for miscarriage management and 437 for miscarriage prevention. METHODS: Modified Delphi method and modified nominal group technique. RESULTS: The final COS for miscarriage management comprises six outcomes: efficacy of treatment, heavy vaginal bleeding, pelvic infection, maternal death, treatment or procedure-related complications, and patient satisfaction. The final COS for miscarriage prevention comprises 12 outcomes: pregnancy loss <24 weeks' gestation, live birth, gestation at birth, pre-term birth, congenital abnormalities, fetal growth restriction, maternal (antenatal) complications, compliance with intervention, patient satisfaction, maternal hospitalisation, neonatal or infant hospitalisation, and neonatal or infant death. Other outcomes identified as important were mental health-related outcomes, future fertility and health economic outcomes. CONCLUSIONS: This study has developed two core outcome sets, through robust methodology, that should be implemented across future randomised trials and systematic reviews in miscarriage management and prevention. This work will help to standardise outcome selection, collection and reporting, and improve the quality and safety of future studies in miscarriage.

Effect of intrauterine infusion of platelet-rich plasma for women with recurrent implantation failure: a systematic review and meta-analysis.

This study evaluated the effect of intrauterine perfusion of autologous platelet-rich plasma (PRP) on pregnancy outcomes in women with recurrent implantation failure (RIF). Key biomedical databases were searched to identify relevant clinical trials and observational studies. Outcomes included clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate, and abortion rate. Data was extracted from ten studies (six randomised controlled trials, four cohort studies) involving 1555 patients. Pregnancy outcomes were improved in women treated with PRP compared to controls: clinical pregnancy rate (RR = 1.96, 95% CI [1.67, 2.31], p < 0.00001, I2 = 46%), chemical pregnancy rate (RR = 1.79, 95% CI [1.54, 2.08], p < 0.00001, I2 = 29%), implantation rate (RR = 1.90, CI [1.50, 2.41], p < 0.00001, I2 = 0%), live birth rate (RR = 2.83, CI [1.45, 5.52], p = 0.0007, I2 = 83%), abortion rate (RR = 0.40, 95% CI [0.18, 0.90], p = 0.03, I2 = 59%). These data imply PRP has potential to improve pregnancy outcomes in women with RIF, suggesting a promising role in assisted reproductive technology.IMPACT STATEMENTWhat is already known on this subject? Platelet-rich plasma (PRP) is an autologous blood product that contains platelets, various growth factors, and cytokines at concentrations above the normal baseline level. Recent studies have shown that intrauterine infusion of autologous PRP can improve pregnancy outcomes in infertile women.What do the results of this study add? This systematic review and meta-analysis of data from ten studies (n = 1555; 775 cases and 780 controls) investigated the effect of intrauterine perfusion of autologous PRP on pregnancy outcomes in women with recurrent implantation failure (RIF). Findings suggest that pregnancy outcomes, including clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate and abortion rate were improved in women treated with PRP compared to controls.What are the implications of these findings for clinical practice and/or further research? RIF remains a challenge for researchers, clinicians, and patients. Our study identified PRP as a potential intervention in assisted reproduction. As an autologous blood preparation, PRP eliminates the risk of an immune response and transmission of disease. PRP is low cost and effective and may represent a new approach to the treatment of patients with RIF.

In vitro-Generated MDSCs Reduce the Pregnancy Complications in an Abortion-Prone Murine Model.

Recurrent spontaneous abortion (RSA) is one of the major pregnancy-related complications. The roles of different immune cells have been studied in pregnancy complications. The current study aimed to investigate myeloid-derived suppressor cells (MDSCs) in a murine abortion model and introduce a therapeutic approach by using in vitro-generated MDSCs in this model. CBA/J × DBA/2 (abortion prone) and CBA/J × Balb/C (normal pregnancy) mice were used. The frequency of granulocytic MDSCs, monocytic MDSCs, and Tregs was checked in the bone marrow and uteroplacental tissue of mice on three gestational days (gd9.5, gd13.5, and gd17.5) using the flow cytometry approach. MDSCs were generated in vitro from bone marrow-isolated cells using GM-CSF and IL-6 cytokines. Abortion-prone mice were injected intravenously with in vitro-generated MDSCs at gd0.5, and pregnancy outcomes were recorded in treated mice. The frequency of G-MDSCs and M-MDSCs in the bone marrow of abortion-prone mice was decreased at gd9.5 (p = 0.026 and p = 0.05, respectively). In uteroplacental tissue, the frequency of G-MDSCs was significantly lower at gd9.5 and gd13.5 (p = 0.001, p = 0.029, respectively), while M-MDSCs only showed decreased number at gd9.5 (p = 0.05) in abortion-prone mice. Injection of in vitro-generated MDSCs resulted in the increased fetus and placenta weights (p = 0.049 and p = 0.012, respectively) but showed no effect on the number of live fetuses and abortion rate. The reduced frequency of both G-MDSCs and M-MDSCs in the bone marrow and at the feto-maternal interface is associated with pregnancy complications. In vitro-generated MDSCs could be considered as a potential approach to reduce these complications.