Intrauterine Treatment Research Articles

Prognosis and outcome of intrauterine treatment of fetuses with critical congenital heart disease.

Intrauterine valvuloplasty is an innovative therapy, which promotes ventricular growth and function in some congenital heart diseases (CHDs). The technique remains challenging and can only be performed in a few centers. This study aimed to assess the feasibility and mid-term outcomes of fetal cardiac intervention (FCI) in fetuses with critical CHD in an experienced tertiary center. Five fetal aortic valvuloplasty (FAV) or fetal pulmonary valvuloplasty (FPV) procedures were performed in our fetal heart center between August 2018 and May 2022. Technical success was defined as crossing the aortic or pulmonary valve and balloon inflation, followed by evidence of increased blood flow across the valve and/or new regurgitation. Follow-up clinical records and echocardiography were obtained during the prenatal and postnatal periods. Five fetuses received FAV or FPV, including critical aortic stenosis ( n = 2) and pulmonary atresia with intact ventricular septum ( n = 3). The mean maternal age was 33.0 ± 2.6 years. The median gestational age (GA) at diagnosis was 24 weeks (range, 22-26 weeks). The median GA at intervention was 29 weeks (range, 28-32 weeks). All five cases underwent successful or partially successful procedures. One patient had pulmonary valve perforation without balloon dilation. No procedure-related deaths or significant complications occurred. However, one neonatal death occurred due to heart and renal failure. The median follow-up period was 29.5 months (range, 8.0-48.0 months). The four surviving patients had achieved biventricular circulation, exhibited improved valve, and ventricular development at the last follow-up visit. Intrauterine FCI could be performed safely with good prognosis in critical CHD.

The Construction of an Intrauterine Diagnosis and Treatment System and Comprehensive Lifecycle Health Service of Congenital Heart Disease: Xinhua Hospital Model

With the growing influence of slow population growth and population aging, China has established the birth policy and issued a series of documents to promote maternal and fetal health and improve the birth rate. With the increase in prevalence of birth defects, timely diagnosis and intervention in utero provide possibilities to reduce unnecessary abortions and offer better prognosis. Congenital heart disease (CHD), as one of the most common congenital birth defects, is the leading cause of mortality in patients aged <5 years, and brings a heavy burden to both the affected families and society. Fetuses with CHD are associated with an increased risk of pregnancy-related complications and premature birth, and children with CHD typically face growth and developmental problems even after the correction of malformation. Therefore, management including diagnosis, treatment, and rehabilitation throughout the fetal period into childhood and even adulthood is essential for children with CHD. Based on the rapid advances in intrauterine and perinatal medicine and an in-depth collaboration among obstetrics and pediatrics, a novel diagnosis and treatment system has been established for the management of CHD in the past 2 decades in Shanghai Xinhua Hospital. This Intrauterine Diagnosis and Treatment System and Comprehensive Lifecycle Health Service of Congenital Heart Disease model provides prenatal diagnosis, intrauterine intervention, delivery room service and neonatal therapies, and postintrauterine rehabilitation for children with CHD. We have developed a four-dimensional spatiotemporal image correlation echocardiography and a three-dimensional cardiac virtual endoscopy system for the intrauterine diagnosis of CHD, dramatically raising the diagnostic utility. Our innovative and independent newborn-intervention technique has effectively reduced the re-intervention rate in patients with pulmonary atresia with intact ventricular septum and critical pulmonary stenosis. In 2018, Xinhua Hospital independently performed the case of fetal aortic valvuloplasty in Asia through a multidepartment collaborative effort. All children treated in this system achieved biventricular circulation and a better long-term postoperative outcome. We also have conducted postoperative rehabilitation therapy to promote the development and health of children with CHD. The practice of Xinhua model has reduced unnecessary abortion of CHD fetuses, reduced the mortality rate associated with critical CHD, and improved the mid- and long-term prognosis in CHD, which is essential to promote the fertility level and children’s health. Furthermore, translational medicine platform and the birth cohort Early Life Plan was constructed to explore the origins of major developmental diseases and establish an early intervention model in CHD. This practice of assessment of the intrauterine system has been expanded to other congenital defects in Xinhua Hospital, and sequential treatment of more than 2,000 cases has been completed to date. Based on practice in intrauterine management of CHD and other diseases, the concept of Intrauterine Pediatrics was proposed as a first to emphasize early prevention and intervention of childhood diseases and promote a comprehensive lifecycle service for children. The development and evolution of this system requires further attention not only from researchers but also from the government and global medical communities.

O-023 ‘The PiNC Trial’: Progesterone in Natural Cycles for the treatment of unexplained infertility

Abstract Study question Does exogenous progesterone for luteal phase support in natural cycles affect the biochemical, clinical pregnancy, livebirth or miscarriage rates in women with unexplained infertility (UI)? Summary answer Progesterone luteal support lead to an increase in livebirth rate from 7% to 15.3% and a decrease in miscarriage rates from 40% to 20%. What is known already Unexplained infertility is a diagnosis likely to encompass a population with varying underlying subtle pathologies. The only treatments currently recommended for treating UI are intrauterine insemination (IUI) and IVF/ICSI which are both expensive and invasive. The evidence for IUI with and without controlled ovarian hyperstimulation (COH) is inconclusive. A recent systematic review and meta-analysis reported a progesterone-mediated reduction in endometrial receptivity as a possible mechanism in the pathogenesis of UI. No trial has been published investigating the effectiveness of exogenous progesterone for luteal support in otherwise natural, unmedicated cycles to improve reproductive outcomes in couples with UI. Study design, size, duration We conducted an open-label, parallel arm, single centre, randomised controlled trial of an investigational medicinal product (cTIMP) from February 2020 to November 2022. We randomised 143 couples with UI to either luteal phase progesterone support or no luteal phase support and analysed the results on an intention-to-treat basis. Each couple participated for 3 menstrual cycles and they were followed up until either the end of a 3rd non-conceptual cycle or any resulting pregnancy. Participants/materials, setting, methods Couples with normal semen analysis (WHO 2020), regular ovulation, bilateral patent tubes, female partner aged ≤42yrs and BMI ≤30 were recruited and randomised following screening and informed consent. Participants timed their luteinising hormone (LH) surge using digital ovulation kits and had timed intercourse for 3 cycles. The treatment group took progesterone suppositories 400mg bd for 14 days after the LH surge. All pregnancies were scanned at 6-7/40 and ongoing pregnancies followed up to delivery. Main results and the role of chance 143 couples were recruited and randomised. Livebirth rates were 11/72 (15.3%) in the treatment group vs. 5/71 (7.0%) in the control group (Odds Ratio (OR) 2.38, 95%CI 0.78-7.24). Biochemical pregnancy rates (defined by a positive urinary pregnancy test) were 15/72 (20.8%) (treatment) vs 10/71 (14.1%) (control) (OR 1.61, 95%CI 0.67-3.86). Clinical pregnancy rates (defined by a gestation sac seen on ultrasound at a minimum of 6/40 gestation) were 14/72 (19.4%) (treatment) vs 9/71 (12.7%) (control) (OR 1.66, 95% CI 0.67-4.13). The miscarriage rate including biochemical losses was 3/15 (20%) of all pregnancies (treatment) vs. 4/10 (40%) (control). One pregnancy in the control group was terminated due to fetal anomalies. There was one ectopic pregnancy in the treatment group. Logistic regression demonstrated that none of the pregnancy outcomes were affected by participant age, BMI, ovarian reserve markers, previous parity or semen analysis parameters. The two participants in the treatment group who experienced miscarriages were both off-protocol. Although the results did not reach statistical significance, the 15.3% livebirth rate and OR of 2.37 for livebirths are clinically significant (equivalent to the success rates of stimulated intrauterine insemination treatment) as is the miscarriage rate of 0/11 clinical intra-uterine pregnancies for women taking progesterone as per protocol.Limitations, reasons for caution Despite the lack of statistical significance, differences in livebirth and miscarriage rates are clinically significant compared with alternative treatments. The trial was unblinded but the objective outcomes are unlikely to be affected by this. A larger trial using the effect size from this study to guide sample size is planned. Wider implications of the findings The treatment investigated here represents a simple, non-invasive and inexpensive option that is acceptable to couples with UI and may increase their chance of pregnancy and livebirth. If this treatment offers similar success rates to stimulated IUI it is likely to become a first-line option for many couple worldwide. Trial registration number 2019-003468-27

A Study of the Literature on Intrauterine Treatment Options for Chronic Placental Insufficiency with Intrauterine Growth Restriction Using Intrauterine Intravascular Amino Acid Supplementation.

Intrauterine growth retardation (IUGR) is a very serious prenatal condition with 3-5% incidence of all pregnancies. It results from numerous factors, including chronic placental insufficiency. IUGR is associated with an increased risk of mortality and morbidity and is considered a major cause of fetal mortality. Currently, treatment options are significantly limited and often result in preterm delivery. Postpartum, IUGR infants also have higher risks of disease and neurological abnormalities. The PubMed database was searched using the keywords "IUGR", "fetal growth restriction", "treatment", "management" and "placental insufficiency" for the period between 1975 and 2023. These terms were also combined together. There were 4160 papers, reviews and articles dealing with the topic of IUGR. In total, only 15 papers directly dealt with a prepartum therapy of IUGR; 10 of these were based on an animal model. Overall, the main focus was on maternal intravenous therapy with amino acids or intraamniotic infusion. Treatment methods have been tested since the 1970s to supplement the fetuses with nutrients lacking due to chronic placental insufficiency in various ways. In some studies, pregnant women were implanted with a subcutaneous intravascular perinatal port system, thus infusing the fetuses with a continuous amino acid solution. Prolongation of pregnancy was achieved, as well as improvement in fetal growth. However, insufficient benefit was observed in infusion with commercial amino acid solution in fetuses below 28 weeks' gestation. The authors attribute this primarily to the enormous variation in amino acid concentrations of the commercially available solutions compared with those observed in the plasma of preterm infants. These different concentrations are particularly important because differences in the fetal brain caused by metabolic changes have been demonstrated in the rabbit model. Several brain metabolites and amino acids were significantly decreased in IUGR brain tissue samples, resulting in abnormal neurodevelopment with decreased brain volume. There are currently only a few studies and case reports with correspondingly low case numbers. Most of the studies refer to prenatal treatment by supplementation of amino acids and nutrients to prolong pregnancy and support fetal growth. However, there is no infusion solution that matches the amino acid concentrations found in fetal plasma. The commercially available solutions have mismatched amino acid concentrations and have not shown sufficient benefit in fetuses below 28 weeks' gestation. More treatment avenues need to be explored and existing ones improved to better treat multifactorial IUGR fetuses.

Experimental treatment of induced fetal retardation in model animals

Intrauterine retardation is one of the major complications of pregnancy. This pathology occurs in approximately 10% of all pregnancies in developed countries and 20% in developing countries. Moreover, intrauterine retardation is more frequently associated with stillbirths than other pathologies. Despite studies conducted in the past 50 years, no generally accepted therapeutic regimen has yet been developed. Numerous drugs have been used for treatment; however, none of them has been proven effective. Moreover, after years of testing, new data are emerging about the side effects of the drugs previously used.
 Various models of fetal retardation have been developed throughout the study of this problem. The main model animals are rats, pigs, and sheep. Numerous techniques and drug options have been proposed for the treatment of simulated intrauterine developmental delays in these animals. The main amino acids used for treatment were arginine, glutamine, taurine, and citrulline. Thus, the literature review aimed to analyze which model animals and experimental models of intrauterine retardation treatment most adequately reflect the effectiveness of these drugs.

A rare case with fetal autoimmune heart block and KNCH2 variant–induced long QT syndrome: a controversial opinion on prenatal management strategy

BackgroundAmong all fetal heart block patients, > 50% cases are associated with maternal autoimmune diseases, and such patients should receive treatment. However, nearly half of fetal heart block cases involve a mother with negative results following autoimmune antibody screening. A few studies have reported long QT syndrome (LQTS) can also present as a severe fetal bradycardia, which does not respond to fetal treatment. Herein, we reported a rare case of an infant who presented with high-degree autoimmune-mediated fetal atrioventricular block (AVB) with LQTS induced by a novel KCNH2 variant. This case led us to review our prenatal therapeutic strategy.Case presentationA 1-year-old boy presented to our heart center having experienced syncope 5 times in the past year. He had previously presented with fetal bradycardia during the fetal stage from 27 + 3 gestational weeks. The fetal echocardiography demonstrated AVB (2:1 transmission). As the maternal autoimmune antibody results were positive, his mother had received dexamethasone treatment during pregnancy; subsequently, the fetal AVB had changed from 2:1 to 4:3 transmission with elevated ventricular beating rates. However, this patient was identified to have complete AVB after birth. The initial electrocardiogram and Holter measurements at hospital administration showed complete AVB, pleomorphic ventricular tachycardia, a prolonged QT interval (QT = 602 ms, corrected QT = 538 ms), and wide and deep inverted T-waves. Meanwhile, torsades de pointes could be observed in several transit ventricular tachycardias based on Holter monitoring review. Genetic testing revealed KCNH2 c.2483G > A variant–induced LQTS. An implantable cardioverter defibrillator device and permanent pacemaker were both considered as therapeutic alternations; his parents ultimately accepted the implantation of a permanent pacemaker.ConclusionsFor fetuses with autoimmune-mediated AVB, intrauterine treatment should still be pursued immediately. However, once the treatment outcomes are deemed unacceptable or unexpected, other genetic variant–related channelopathies should be highly suspected. If the fetus lacks a positive family history, fetal genetic testing should be recommended to improve the prognosis of such patients by introducing integrative therapeutic strategies between the prenatal and postnatal phases.

Fetal urinary ascites due to posterior urethral valve: A case report

Introduction: Urinary peritonitis is a rare event that can occur most often in congenital malformation of posterior urethral valves (PUVs) due to bladder rupture or upper urinary tract. This malformation is most common in male newborns. The prognosis depends on the degree of oligohydramnios and precocity of installation with which posterior urethral valve is always associated. It is a factor that affects significantly the intrauterine development of the lungs and the severity of kidney impairment. Nowadays, diagnosis is prenatally possible, which leads to early intrauterine treatment with urinary decongestion, thus prognosis is significantly improved. Case Report: In this paper we talk about the case of a male fetus with posterior urethral valve manifested as fetal ascites after rupture of the urinary bladder wall giving rise to urinary peritonitis. Conclusion: The ultrasound diagnosis of fetal ascites is relatively easy; however, some images may incorrectly lead to the diagnosis of fetal ascites that’s why it is important to know them as well as the different etiologies.

Fetal NT-proBNP levels and their course in severe anemia during intrauterine treatment

PurposeIn adults and fetuses, N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac failure and myocardial remodelling. We examined the effect of anemia and intrauterine transfusion (IUT) on NT-proBNP concentrations in fetuses with anemia and established gestational age-dependent reference values of a control group.MethodsWe analyzed NT-proBNP levels in anemic fetuses that underwent serial intrauterine transfusions (IUT), focusing on different causes and severity of anemia and comparing the results to a non-anemic control group.ResultsIn the control group, the average NT-proBNP concentration was 1339 ± 639 pg/ml, decreasing significantly with increasing gestational age (R = − 74.04, T = − 3.65, p = 0.001). Subjects had significantly higher NT-proBNP concentrations before initiation of IUT therapy (p < 0.001), showing fetuses with parvovirus B19 (PVB19) infection having the highest concentrations. Hydropic fetuses also showed an increased NT-proBNP concentration compared to non-hydropic fetuses (p < 0.001). During the course of therapy, NT-proBNP concentration before subsequent IUT decreased significantly from pathologically high levels, while MoM-Hb and MoM-MCA-PSV remained pathological.ConclusionNT-pro BNP levels in non-anemic fetuses are higher than in postnatal life, decreasing with ongoing pregnancy. Anemia is a hyperdynamic state and its severity correlates with circulating NT-proBNP levels. Highest concentrations occur in fetuses with hydrops and with PVB19 infection, respectively. Treatment by IUT leads to a normalisation of NT-proBNP concentrations, so the measurement of its levels may be useful in therapy monitoring.

Fetal Hemoglobin H Hydrops Fetalis: Another Three Case Reports

We report three cases of fetalis hydrops associated with nondeletional α-thalassemia. Two cases were caused by hemoglobin (Hb) H-Quong Sz disease, and one caused by homozygous Hb Constant Spring. Fetal hydrops occurred in the late second trimester in all three cases. Our study indicates that for pregnancies at risk for fetal nondeletional Hb H disease, strict ultrasound follow-up is particularly important. Even without techniques of intrauterine transfusion treatment, early prenatal diagnosis can enable parents to make timely decisions.

Comparison of systemic trimethoprim-sulfadimethoxine treatment and intrauterine ozone application as possible therapies for bacterial endometritis in equine practice.

Bacterial endometritis is one of the major problems in equine reproduction and usually treated with antimicrobial drugs. The study aimed to compare the effects of intrauterine ozone application and systemic antibiotic treatment (trimethoprim-sulfadimethoxine) on intrauterine bacterial growth and possible side effects on the endometrium in a clinical setting. Mares (n = 30) with signs of endometritis (positive uterine bacterial culture and cytological findings) were assigned randomly to different treatments: intrauterine insufflation of an ozone-air-mix (240 ml, 80 μg ozone/ml) twice at a 48 h-interval (Ozone; n = 10), systemic antibiotic therapy with trimethoprim-sulfadimethoxine (30 mg/kg, p.o., twice daily) for 5 days (TMS; n = 10), or intrauterine insufflation of air (240 ml, sterile-filtered) twice at a 48 h-interval (air; n = 10). Endometrial biopsy for histological examination was obtained before the treatment. Histological examination revealed no differences among groups. A control examination, including transrectal ultrasound, bacterial culture, cytological evaluation, and biopsy, was performed 7 days after the last treatment. Overall bacterial growth was reduced in every group after the treatment (p < 0.05), irrespective of the therapy [Ozone: 4/9 (positive culture after treatment/number of mares), TMS: 3/10 and Air: 6/10; p > 0.05]. However, Ozone and TMS (p < 0.05) were more effective in reducing growth of gram-negative bacteria as compared to Air (p > 0.05). No effects on the number of polymorphonuclear granulocytes (cytology) were observed (p > 0.05). In conclusion, trimethoprim-sulfadimethoxine and intrauterine ozone insufflation are safe treatment options for bacterial endometritis in mares but the efficacy of both treatments in reducing bacterial growth did not result in a complete absence of intrauterine bacterial growth.

Intrauterine tablet treatment accompanied with parenteral application of ceftiofur in enhancing of reproductive effectiveness of dairy cows in the municipality of Sanski Most

Intrauterine tablet treatment accompanied with parenteral application of ceftiofur in enhancing of reproductive effectiveness of dairy cows in the municipality of Sanski Most

Comparison of Adjunctive Use of G-CSF Vs Autologous PRP in IVF Patients with a Refractory Thin Endometrium: A Retrospective Record Review

Background: In Vitro Fertilization (IVF) is an important treatment option in the management of couples with infertility. Sadly, however, failure to achieve a pregnancy through IVF is not uncommon. Amongst the many causes of IVF failure, implantation failure has emerged as one of the more common and important factors. The refractory thin endometrium as a cause of recurrent IVF failure has been well documented. The use of either Granulocyte Colony Stimulating Factor (G-CSF) or autologous Platelet Rich Plasma (PRP) has emerged as potential adjunctive treatments that may mitigate the rate of implantation failure; however, no conclusive evidence exists to favour the use of one over the other. Objective: To compare the measured change in endometrial thickness and pregnancy rates in patients with Recurrent implantation Failure (RIF) and/or thin endometrium following the intrauterine administration of either G-CSF or autologous PRP. In addition, to compare the pregnancy rates in patients with fluid in the endometrial cavity who underwent either therapy. Design: A retrospective analysis was conducted on patients who underwent endometrial therapy (either G-CSF or PRP) between January and June 2020. The measured change in endometrial thickness and the clinical pregnancy outcome of the two groups were compared. Subjects: 36 patients with a mean age of 40.36 years met the inclusion criteria of the study. 20 received autologous intrauterine PRP treatment and 16 received intrauterine G-CSF treatment. Both groups were well matched for age, pre-intervention endometrial thickness and embryo quality. Intervention: Administration of G-CSF (One ampoule Neupogen® (filgrastim)) or PRP (1ml) into the uterine cavity transcervical 48 hours prior to embryo transfer. Main Outcome Measures: The change in endometrial thickness measured 48 hours prior to embryo transfer and at the time of embryo transfer (ET) was compared. Positive clinical pregnancy outcome was determined by a positive serum B-HCG test 10 days post insertion. A statistically significant difference was set at p=0.05. Results: There was a statistically significant difference in endometrial expansion post intervention in both the G-CSF and PRP groups. However, the difference between the two groups did not reach statistical significance (p=0.077). Additionally, the collective pregnancy rate of the total study population was 44.4% (16 of 36), a significant increase over the expected pregnancy rate in the published literature [1,2]. Of the positive pregnancies, 9 (56.25%) were in the autologous PRP group and 7 (43.75%) in the G-CSF group. This difference was, however, determined not to be statistically significant (p=0.603). Conclusion: Both G-CSF and PRP are effective interventions in the management of the thin refractory endometrium. Both result in significant endometrial expansion and increased pregnancy rates. Despite a marginally higher endometrial response and pregnancy rate in the PRP group, the differences in these metrics between the two groups were not statistically significant.

Flexible treatment of gestational diabetes mellitus adjusted according to intrauterine fetal growth versus treatment according to strict maternal glycemic parameters: a randomized clinical trial

IntroductionTo compare the conventional treatment of gestational diabetes mellitus (GDM) with flexible treatment according to the measurement of fetal abdominal circumference (AC) in daily clinical practice.Research design and methodsTwo hundred...

Successful intra‐amniotic levothyroxine treatment for fetal goitrous hypothyroidism in a triplet pregnancy

We report an extremely challenging case of fetal goitrous hypothyroidism involving all three fetuses of a triplet pregnancy in which successful fetal treatment led to a favorable pregnancy outcome. The patient had a trichorionic, triamniotic triplet pregnancy and was referred to us at 24 weeks gestation after goiters affecting all three fetuses and polyhydramnios involving two fetuses were noted. Immediately before the conception, she underwent hysterosalpingography with an oil-soluble iodinated contrast medium. After the diagnosis of fetal hypothyroidism was made, intra-amniotic injection of levothyroxine was performed for two fetuses with polyhydramnios 3 times between 28 and 31 weeks gestation. The goiters shrunk and the polyhydramnios improved in response to the in utero treatment. No complications occurred. Cesarean section was performed at 33 weeks gestation. None of the three neonates developed respiratory insufficiency. Our experience suggested that successful intrauterine treatment is possible for fetal goitrous hypothyroidism, even in a triplet pregnancy. The indication, treatment timing, and diagnostic and assessment strategies should be carefully discussed to minimize puncture-related complications.

The efficacy and safety of luteal phase support with progesterone following ovarian stimulation and intrauterine insemination: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to update the current evidence for the efficacy and safety of progesterone luteal phase support (LPS) following ovarian stimulation and intrauterine insemination treatment (OS-IUI) for unexplained or mild male infertility. Four additional studies were identified compared to the previous review in 2017. Twelve RCTs (2631 patients, 3262 cycles) met full inclusion criteria. Results from quantitative synthesis suggest that progesterone LPS after OS-IUI leads to higher live birth (RR 1.38, 95%CI [1.09, 1.74]; 7 RCTs, n=1748) and clinical pregnancy rates (RR 1.38, 95% CI [1.21, 1.59]; 11 RCTs, n=2163) than no LPS or placebo. This effect is specifically present in protocols using gonadotropins for OS-IUI (RR 1.41, 95%CI [1.17, 1.71]; 7 RCTs, n=1114), and unclear in protocols involving clomiphene citrate (RR 1.01, 95% CI [0.05, 18.94]; 2 RCTs, n=138). We found no effect of progesterone LPS on multiple pregnancy or miscarriage rates. No correlation between drug-dosage or duration of treatment and effect size was seen. Though our results suggest both benefit and safety of progesterone LPS in OS-IUI, evidence is of low to moderate quality and additional well-powered trials are still mandatory to confirm our findings and justify implementation in daily practice.Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=292325, identifier CRD42021292325.

Estradiol and intrauterine device treatment for moderate and severe intrauterine adhesions after transcervical resection

ObjectiveTo explore the effect of 4 mg/day, 6 mg/day, and 8 mg/day estradiol alone or in combination with an intrauterine device (IUD) in patients with moderate and severe intrauterine adhesion (IUA) after transcervical resection of adhesion (TCRA).MethodsPatients with moderate or severe IUA who reived 4 mg/day, 6 mg/day, and 8 mg/day estradiol alone or in combination with an intrauterine device (IUD) after TCRA in Women’s Hospital, Zhejiang University School of Medicine, from March 2014 to December 2014 were enrolled in this retrospective case–control study. In group A, 14 patients received estradiol 4 mg/day + IUD after the first operation; in group B, 29 patients (group B0) received estradiol 6 mg/day after the first operation, and 73 patients (group B1) received estradiol 6 mg/day + IUD; in group C, 14 patients received estradiol 8 mg/day + IUD after the first operation. Referring to ESGE's IUA diagnostic classification method, 72 patients had moderate adhesion, and 58 cases had severe adhesion. Outpatient follow-up was performed at 1 and 23 months and after 1 year. The postoperative menstrual improvement, uterine cavity recovery, drug side effects at two to three months, and pregnancy situation at one year were recorded.ResultsThere were no significant differences in age, BMI, and previous intrauterine operation times between the 3 groups (all p > 0.05). Compared with Group A, more patients in group C had severe IUA (p = 0.008). In addition, there were no differences in menstrual recovery, uterine cavity recovery, and pregnancy in one year between the 3 groups (p > 0.05) and between groups B0 and B1 (p > 0.05). In group B1, 51 (69.86%) patients had IUD incarceration.ConclusionThis data suggests that 4 mg/d doses of estrogen may have the same effect in improving the menstrual condition, uterine cavity morphology, and reproductive ability compared to a higher dosage (6 mg/day estrogen and 8 mg/day). In addition, the placement of IUD in the uterine cavity during TCRA may cause IUD incarceration, and the treatment results for the prevention of IUA are not better than without IUD.

Developmental programming of mitochondrial substrate metabolism in skeletal muscle of adult sheep by cortisol exposure before birth.

Prenatal glucocorticoid overexposure causes adult metabolic dysfunction in several species but its effects on adult mitochondrial function remain largely unknown. Using respirometry, this study examined mitochondrial substrate metabolism of fetal and adult ovine biceps femoris (BF) and semitendinosus (ST) muscles after cortisol infusion before birth. Physiological increases in fetal cortisol concentrations pre-term induced muscle- and substrate-specific changes in mitochondrial oxidative phosphorylation capacity in adulthood. These changes were accompanied by muscle-specific alterations in protein content, fibre composition and abundance of the mitochondrial electron transfer system (ETS) complexes. In adult ST, respiration using palmitoyl-carnitine and malate was increased after fetal cortisol treatment but not with other substrate combinations. There were also significant increases in protein content and reductions in the abundance of all four ETS complexes, but not ATP synthase, in the ST of adults receiving cortisol prenatally. In adult BF, intrauterine cortisol treatment had no effect on protein content, respiratory rates, ETS complex abundances or ATP synthase. Activity of citrate synthase, a marker of mitochondrial content, was unaffected by intrauterine treatment in both adult muscles. In the ST but not BF, respiratory rates using all substrate combinations were significantly lower in the adults than fetuses, predominantly in the saline-infused controls. The ontogenic and cortisol-induced changes in mitochondrial function were, therefore, more pronounced in the ST than BF muscle. Collectively, the results show that fetal cortisol overexposure programmes mitochondrial substrate metabolism in specific adult muscles with potential consequences for adult metabolism and energetics.

Clinical Evaluation of Autologous and Allogeneic Stem Cell Therapy for Intrauterine Adhesions: A Systematic Review and Meta-Analysis.

ObjectiveIntrauterine adhesions (IUAs) are a major cause of female infertility. Stem cells can be used to restore endometrial function owing to their regenerative abilities. We compared the safety and efficacy of autologous and allogeneic stem cell treatments in patients with recurrent IUA after conventional therapy based on a systematic review of the related literature.MethodsThe PubMed, Embase, and Cochrane databases were systematically searched. All analysis were performed using Review Manager 5.4. We compared improvements in endometrial thickness, pregnancy rates, menstruation, and side effects after autologous and allogeneic stem cell therapy. The study was registered with PROSPERO, CRD 42022322870.ResultsOur search returned 154 reports, 10 of which met the inclusion criteria, representing 116 patients. Of these, 44 patients in two studies were treated with allogeneic stem cells and 72 patients in eight studies were treated with autologous stem cells. Improvements in endometrial thickness and pregnancy rates after intrauterine device treatment were compared between the autologous and allogeneic stem cell groups. Endometrial thickness increased more after autologous stem cell IUA treatment (mean difference, 1.68; 95% confidence interval [CI]: 1.30–2.07; P < 0.00001), and the pregnancy rate was also improved (relative risk, 1.55; 95% CI: 1.19–2.02, P < 0. 001). No obvious and serious adverse reactions were observed during stem cell therapy in either group.ConclusionsThis meta-analysis and systematic review of the results of randomized trials of autologous and allogeneic stem cell treatments for IUA suggests that autologous stem cells have a better effect in improving the endometrium thickness and pregnancy rate.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022322870.

Hemolytic disease of the newborn, beyond the Rhesus disease

Hemolytic disease of the fetus and newborn is a consequence of maternal immune response to fetal red blood cells antigens inherited from the father, that the mother does not possess, stimulated by antepartum or intrapartum fetomaternal hemorrhage. As a result, fetal erythrocytes are destroyed, leading to various degrees of anemia and hyperbilirubinemia, with high perinatal morbidity and mortality rates. This review’s purpose is to reveal the importance of the alloantibodies beyond RhD and ABO system, the updated algorithms used in the diagnosis and management of the disease and the importance of RhD universal immune prophylaxis practice. For this purpose, the database from PubMed and UpToDate was searched for literature reviews, case studies, society guidelines and retrospective studies in English regarding hemolytic disease of the fetus and newborn from 2013 to March 2022. Anti D prophylaxis protocols, early diagnosis and proper intrauterine and postpartum treatment help significantly reduce the disease’s burden.

Recent Developments in Biomaterial-Based Hydrogel as the Delivery System for Repairing Endometrial Injury.

Endometrial injury caused by intrauterine surgery often leads to pathophysiological changes in the intrauterine environment, resulting in infertility in women of childbearing age. However, clinical treatment strategies, especially for moderate to severe injuries, often fail to provide satisfactory therapeutic effects and pregnancy outcomes. With the development of reproductive medicine and materials engineering, researchers have developed bioactive hydrogel materials, which can be used as a physical anti-adhesion barrier alone or as functional delivery systems for intrauterine injury treatment by loading stem cells or various active substances. Studies have demonstrated that the biomaterial-based hydrogel delivery system can provide sufficient mechanical support and improve the intrauterine microenvironment, enhance the delivery efficiency of therapeutic agents, prolong intrauterine retention time, and perform efficiently targeted repair compared with ordinary drug therapy or stem cell therapy. It shows the promising application prospects of the hydrogel delivery system in reproductive medicine. Herein, we review the recent advances in endometrial repair methods, focusing on the current application status of biomaterial-based hydrogel delivery systems in intrauterine injury repair, including preparation principles, therapeutic efficacy, repair mechanisms, and current limitations and development perspectives.