Miscarriage Rate Research Articles

Impact of the ARRIVE Trial on Stillbirth Rates in Nulliparous Individuals.

We aim to examine the population-level rates of induction, stillbirth, perinatal mortality, and neonatal death before and after the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial. This study was a cross-sectional analysis of publicly available U.S. Live Birth data linked with Infant Death and Fetal Death certificate data from National Vital Statistics Online. We limited analyses to nulliparous individuals with singleton pregnancy and cephalic presentation who delivered at 39 weeks or greater. The pre- and post-ARRIVE periods spanned from August 2016 to July 2018, and from January 2019 to December 2020, respectively. Our primary outcome was a stillbirth. Secondary outcomes included induction of labor, perinatal mortality, and neonatal death. Outcomes were compared between the pre- and post-ARRIVE periods. Modified Poisson regression was used to calculate adjusted relative risks (aRRs). Of 2,817,071 births, there were 1,454,346 births in the pre-ARRIVE period and 1,362,725 in the post-ARRIVE period; there were 1,196 and 1,062 stillbirths in the pre- and post-ARRIVE periods, respectively. Compared to the pre-ARRIVE period, the post-ARRIVE period was not associated with a significant decrease in the risk of stillbirth at 39 weeks or greater (aRR 0.92 [95% confidence interval {95% CI} 0.85-1.00]) and stillbirth at 40 weeks or greater (aRR 0.92 [95% CI 0.82-1.04]). Compared to the pre-ARRIVE trial period, the post-ARRIVE trial was associated with increased rates of induction of labor at 39 weeks (aRR 1.37 [95% CI 1.37-1.38]) and 40 weeks (aRR 1.24 [95% CI 1.24-1.25]. Similar to stillbirth, there was no significant decrease in the risk of perinatal mortality at 39 weeks or greater or 40 weeks or greater. There was also no statistically significant change in neonatal death rates at 39 weeks or greater or at 40 weeks or greater. The increase in induction of labor at 39 weeks was not large enough to impact the stillbirth rate at 39 weeks or greater. · Post-ARRIVE trial, rate of induction of labor increased at 39 and 40 weeks.. · Post-ARRIVE trial, stillbirth and perinatal mortality rates remained unchanged.. · Induction rate rise post-ARRIVE trial did not impact neonatal death rates..

Sperm chromatin dispersion assay reliability and assisted reproductive technology outcomes: Systematic review and meta-analysis.

Elevated sperm DNA fragmentation has potential implications for semen quality and fertility. The commonly used sperm chromatin dispersion test offers an indirect estimation but has limitations in terms of bias and variability. This study aimed to assess the reliability of the sperm chromatin dispersion assay for predicting assisted reproductive technology outcomes. This systematic review included studies published until December 2023 that adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, Scopus, and Google Scholar databases were searched. Various assisted reproductive technology outcomes in patients with high (≥30%) versus low (<30%) sperm DNA fragmentation were compared using a sperm chromatin dispersion assay and including a sub-analysis of intracytoplasmic sperm injection versus in vitro fertilization. A comprehensive meta-analysis software facilitated quantitative analysis with statistical comparisons between cases and controls. Interstudy heterogeneity was assessed, and sensitivity and publication bias tests were performed. Of the 199 abstracts assessed, 64 full-text articles were screened, and 44 articles were qualitatively synthesized. Fourteen articles representing 5346 participants were quantitatively analyzed. Using the sperm chromatin dispersion assay, elevated sperm DNA fragmentation was associated with lower fertilization and embryo cleavage rates. Notably, high sperm DNA fragmentation levels did not affect the clinical pregnancy, implantation, miscarriage, or live birth outcomes. Sub-analysis revealed lower fertilization, embryo cleavage, clinical pregnancy, live birth rates, and higher miscarriage rates in the intracytoplasmic sperm injection subgroup only. The sperm chromatin dispersion assay did not show significant differences in pregnancy or live birth rates between the high- and low-sperm DNA fragmentation groups. Noteworthy, high sperm DNA fragmentation was associated with worse assisted reproductive technology outcomes in the intracytoplasmic sperm injection group. Given the current quality of the evidence, affected by the experimental design and the absence of correction for female factors of infertility, clinicians should be wary of the assay's limited predictive power for pregnancy and live birth outcomes.

Epidemiology and Outcomes of Hepatitis E Virus-Associated Hospitalisations in the United States With a Focus on Pregnancy: A Nationwide Population Study, 1998-2020.

Hepatitis E virus (HEV) is typically asymptomatic in developed countries but can be more severe in certain populations. We aim to describe the epidemiology of HEV-associated hospitalisations from 1998 to 2020 in the United States, investigate risk factors for inpatient mortality and describe outcomes in pregnant women. We utilised the National Inpatient Sample and extracted cases of HEV-associated hospitalisations using ICD-9/10 diagnostic codes. Demographic, clinical and pregnancy data were extracted and analysed by chi-square and logistic regression. We identified 3354 cases of HEV-associated hospitalisations; 1689 (50.4%) were female and 1425 (42.5%) were non-Hispanic White. The median age was 50 (IQR: 37-59) years. Hospitalisation rates for HEV ranged from 2.5 per 10,000,000 in 2008 to a peak of 9.6 per 10,000,000 people in the general U.S. population in 2004. The mortality rate was 5.2%. Age ≥ 40 years (OR: 7.73; 95% CI: 1.57-38.09; p = 0.012), HIV infection (OR: 4.63; 95% CI: 1.26-16.97; p = 0.021), and coagulopathy (OR: 7.22; 95% CI: 2.81-18.57; p < 0.001) were associated with increased odds of mortality within the HEV cohort. There were 226 pregnant women with HEV. Rates of maternal death, stillbirth and preterm birth were similar between HEV and non-HEV pregnant cohorts. Hepatitis B and hepatitis C co-infection were significantly more common in the HEV pregnant cohort (p < 0.05). HEV-associated hospitalisations are uncommon in the United States, but likely underdiagnosed. Certain risk factors can be used to predict prognosis of these hospitalised patients. Pregnant women with HEV appear to have favourable maternal and fetal outcomes despite hepatitis B and C co-infection.

Impact of intrapartum quality improvement interventions on stillbirths and other adverse pregnancy outcomes: A protocol for systematic review and meta-analysis.

Stillbirths are a major global health concern. Half of stillbirths occur during intrapartum period, mostly in low- and middle-income countries of sub-Saharan Africa and South Asia. Achieving a stillbirth rate of less than 12 per 1000 births by 2030 is the global target of Every Newborn Action Plan and Sustainable Development Goals. Evidence suggests that improving intrapartum quality of care can help reduce stillbirths and other adverse pregnancy outcomes. This study will explore whether quality improvement (QI) packages at intrapartum care points can reduce stillbirths and other outcomes such as maternal and neonatal mortality. We will conduct a systematic literature review and meta-analysis. Comprehensive search strategy will be developed for databases PubMed, Web of Science, ScienceDirect, ProQuest, Cochrane and China National Knowledge Infrastructure. We will include randomized controlled trials, controlled non-randomized trials, controlled clinical trials, interrupted time series, cohort studies, case-control and nested case-control studies which assess the impact of QI interventions at intrapartum points of care on stillbirths and other adverse pregnancy outcomes. We will search grey literature such as unpublished research studies, dissertations and unfinished trials. English and non-English language articles will be included to avoid language bias. We will also evaluate reporting quality and risk of bias. Sensitivity tests will be carried out for heterogeneity. Pooled estimates of effect sizes will be computed with random-effects models. Supplementation of the quantitative synthesis with a qualitative narrative synthesis would be added, if deemed necessary. We will explore publication bias using funnel plot and Egger's regression test will be used for evaluation, if needed. We will report pooled effectiveness of different intrapartum QI interventions across multiple settings in averting stillbirths and other adverse outcomes such as maternal mortality and neonatal mortality.

Reproductive outcomes in women with advanced endometriosis in fresh versus frozen embryo transfer cycles

BackgroundART in women with endometriosis is associated with poor quality of the retrieved oocytes and lower fertilization and pregnancy rates, reflecting that endometriosis may influence fertility by altering the quality of both the oocyte and embryo quality and also by impairing the endometrial receptivity. On comparing endometriosis-affected patients to healthy counterparts, many differences were demonstrated at the endometrial level. Thus, choosing the appropriate method of embryo transfer is of utmost importance, particularly for patients with advanced endometriosis.ObjectiveThe aim of the present study was to compare the reproductive outcomes between fresh and frozen embryo transfer cycles in women with advanced endometriosis.Material and methodsA retrospective cohort study was conducted in the period from January 2018 until December 2021 for patients recruited from two IVF centers, Alexandria, Egypt. Careful review of paper and electronic medical records of infertile women (primary, relative, or secondary infertility) aged 18–37 years who were diagnosed with advanced endometriosis by means of laparoscopy and were scheduled for ICSI followed by either fresh embryo transfer (group I) or freeze-all embryos and deferred embryo transfer (group II) of day 5 embryo(s) was included in the study.ResultsTwo-hundred and eleven women were eligible and included in the study. Women in each study group were matched regarding baseline characteristics. Clinical pregnancy, implantation, and ongoing pregnancy rates were statistically significantly higher in the group of frozen embryo transfer (p < 0.001). Miscarriage rate was found to be higher in the group of fresh transfer compared to FET group but without a statistical significance (20.9% vs 9.2%, p = 0.072).ConclusionIn women with advanced endometriosis, freeze-all policy seems to be associated with better implantation, ongoing pregnancy rates.

Assessment of Caesarean Section Outcomes for Preterm Pregnancies in a Tertiary Care Hospital in Bangladesh

A cross-sectional, observational study was conducted in the Department of Obstetrics and Gynaecology at Community Based Medical College, Bangladesh (CBMC,B), Mymensingh, Bangladesh, to evaluate the indications and feto-maternal outcomes of Caesarean section operation among preterm pregnant women. A total of 120 patients were enrolled between January and December of 2023. Data collection involved a structured questionnaire, file review, historical inquiry, and monitoring of mother and baby. Most individuals were aged 15-20 (37.50%) and had tertiary education (75.00%). Majority were from poor socio-economic backgrounds (76.67%) and rural areas (70%). Primigravida cases were predominant (65.00%), and multiparous accounted for 36.67%. Eclampsia (21.67%) and preeclampsia (20.83%) were common indications for cesarean section. Most procedures were emergency (93.33%). Maternal complications were low, with 64.17% having none. Most infants had low birth weight (62.50%) and experienced live births (91.67%), with a notable stillbirth rate (8.33%). Fetal complications included low birth weight (88.33%) and prematurity (20%). No complications were noted in 31.67% of cases. The study examined the complexities of Cesarean section (CS) for preterm births, highlighting maternal-fetal factors, varied indications, and outcomes, urging tailored interventions. CBMJ 2024 July: vol. 13 no. 02 P: 243-250

Fetal major anomalies and related maternal, obstetrical, and neonatal outcomes.

To examine maternal, obstetrical, and neonatal outcomes of pregnancies complicated by major fetal anomalies. A 10year retrospective cohort study at a tertiary university hospital compared maternal and obstetrical outcomes between women with singleton pregnancies complicated by major fetal anomalies, and a control group with non-anomalous fetuses. For the study compared to the control group, the median gestational age at delivery was lower: 37.0 vs. 39.4weeks (p < 0.001); and the preterm delivery rates were higher, both at < 37weeks (46.2 vs. 6.2%, p < 0.001) and < 32weeks (15.4 vs. 1.2%, p < 0.001). For the study compared to the control group, the placental abruption rate was higher (6.8 vs. 0.9%, p = 0.002); 87.5 vs. 100% occurred before labor. For the respective groups, the mean gestational ages at abruption were 32.8 ± 1.3 and 39.9 ± 1.7weeks (p = 0.024); and cesarean section and postpartum hemorrhage rates were: 53.8 vs. 28.3% (p < 0.001) and 11.3 vs. 2.8% (p = 0.001), respectively. For the respective groups, hypertensive disorders of pregnancy rates were 9.5 vs. 2.1% (p = 0.004), stillbirth rates were 17.1 vs. 0.3% (p < 0.001), and neonatal death rates 12.5 vs. 0.0% (p < 0.001). Major fetal anomalies were found to be associated with adverse maternal outcomes (OR = 2.47, 95% CI 1.50-4.09, p < 0.001). Polyhydramnios was identified as an independent risk factor in a multivariate analysis that adjusted for fetal anomalies, conception by IVF, and primiparity for adverse maternal outcomes (OR = 4.7, 95% CI 1.7-13.6, p < 0.001). Pregnancies with major fetal anomalies should be treated as high-risk due to the increased likelihood of adverse maternal and neonatal outcomes.

Patient with Herlyn–Werner–Wunderlich syndrome and endometriosis achieves successful full-term pregnancy (40 weeks and 6 days): a case report

IntroductionHerlyn–Werner–Wunderlich syndrome , a rare Müllerian ducts congenital disease, is characterized by a diphtheritic uterus, blind hemivagina, and ipsilateral renal agenesis. Diagnosis is at young age by ultrasound and magnetic resonance imaging, and the prognosis is good. Usually, complications evolve endometriosis and secondary pelvic inflammation.Case reportA 40-year-old female patient, Brazilian, white, primigravida, diagnosed at 30 years with a didelphic uterus on ultrasound, and 4 years later, with a left ovarian endometrioma, multiple ovarian cysts, and left renal agenesis on magnetic resonance imaging. Subsequently, due to dyspareunia and a feeling of swelling, the patient underwent transvaginal ultrasound with bowel preparation, and a hematocolpos was found and Herlyn–Werner–Wunderlich syndrome was suspected; 10 years after the diagnosis she had a planned pregnancy. She presented frequent contractions following the 15th week of pregnancy and fortunately there were no complications or premature labor. Labor was inducted at 40 weeks and 6 days without progress and a cesarean section was indicated and performed without complications. Herlyn–Werner–Wunderlich syndrome often goes unnoticed, leading to inadequate treatment. Individuals with Herlyn–Werner–Wunderlich syndrome commonly face fertility issues, such as high miscarriage rate (21–33%), and obstetric complications, such as spontaneous abortions (40% risk), intrauterine growth restriction, postpartum hemorrhage, increased fetal mortality, preterm delivery (21–29%), and elevated rates of cesarean sections. In addition, there is higher susceptibility of developing endometriosis, especially with hemivaginal obstruction, and pelvic adhesions.ConclusionEarly diagnosis enables timely treatment and, consequently, fewer complications. Still, when these factors are absent, vaginal birth may still be possible. The true prevalence and incidence of complications related to Herlyn–Werner–Wunderlich syndrome are still unknown.

Subcutaneous G-CSF administration improves IVF outcomes in patients with recurrent implantation failure presenting a KIR/HLA-C mismatch

Research questionDespite advances in assisted reproductive technologies, many blastocysts are lost unexpectedly during implantation. Alterations in maternal immune tolerance towards fetal antigens may contribute to adverse IVF outcomes. The purpose of this study is to evaluate whether administering Granulocyte Colony-Stimulating Factor (G-CSF) to couples with a Human Leukocyte Antigen/Killer-Cell Immunoglobulin-Like Receptor (HLA/KIR) mismatch could positively modulate the implantation process in patients with recurrent implantation failure (RIF). A KIR/HLA-C mismatch occurs when the interaction between KIRs and HLA-C causes an inhibition of NK cells, which may result in reduced G-CSF secretion leading to impaired placentation and increased risk of miscarriage, pre-eclampsia and fetal growth restriction. DesignA retrospective monocentric cohort study conducted at the IVI Clinic in Rome, including women with a history of at least two failed blastocyst transfers. Couples underwent KIR and HLA-C testing. Couples with a KIR/HLA-C mismatch received G-CSF subcutaneously up to week nine of gestation. The mismatch included cases with inhibitory KIR genotypes and HLA-C2C2 females with HLA-C1C1, or C1C2 males or HLA-C1C2 females with male HLA-C2C2. The reproductive outcomes were assessed, and the logistic regression models controlled for potential confounders affecting IVF outcomes. Results79 patients with RIF and a KIR/HLA-C mismatch were included in the study. 30 patients were administered G-CSF, and 49 received no treatment. In the univariate analysis, no statistically significant differences were reported in the reproductive outcomes after IVF between the women treated with G-CSF and the control group. However, the logistic regression analysis that controlled for confounding factors showed that patients treated with subcutaneous G-CSF had statistically significant higher ongoing-pregnancy (aOR=3.808) and live-birth (aOR=4.998) rates, and a lower miscarriage rate (aOR=0.057). No statistically significant differences were found in other reproductive outcomes. ConclusionThe use of subcutaneous G-CSF in patients with a KIR/HLA-C mismatch undergoing IVF may reduce miscarriage and improve live-birth rates. G-CSF may modulate NK-mediated immune mechanisms and improve trophoblast invasion and development. Randomized trials are warranted to validate these findings and enhance the chances of successful pregnancies in couples with an immunological mismatch.

The Effect of Nutrient Supplementation on Female Fertility: A Systematic Review.

Assisted reproductive technologies (ART) have improved infertility treatmentbut reproductive outcomes remain challenging. Nutrient supplementation is being explored to enhance pregnancy rates, increase live birth rates, and reduce miscarriage rates in females undergoing ART. Nutrients like folic acid, omega-3 fatty acids, and antioxidants have shown potential benefits, yet conflicting results exist. Live birth rates may also be influenced by nutrient supplementation, with coenzyme Q10 and vitamin D showing promise. Miscarriage rates may be reduced with nutrients such as vitamin D, omega-3 fatty acids, and antioxidants, although more research is needed for definitive conclusions. Scientific and medical literature databases such as Cochrane Library, PubMed, and Web of Science were queried to identify relevant English publications adhering to predetermined inclusion and exclusion criteria. Various reproductive metrics, encompassing biochemical pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, implantation rate, live birth rates, and miscarriage rates, were assessed as clinical endpoints.The study population included 996 female subjects receiving ART. Two studies performed investigations on subjects diagnosed with unexplained infertility, two studies specifically included polycystic ovary syndrome patients, and five studies did not provide any specific information on the type of infertility or subfertility. All studies reported on the clinical/ongoing pregnancy rate, among which four included studies observed a significantly higher rate. Out of the four studies that reported on implantation rates, three found significantly higher rates in treatment groups. Out of the three studies that reported on biochemical pregnancy rates, two studies found significantly higher rates in treatment groups. With respect to the clinical outcomes that were studied in this analysis, variable effects of nutritional supplementation on reproductive parameters were observed. Some studies reported significantly higher rates of clinical/ongoing pregnancy, implantation, biochemical pregnancy, and live birth, while no significant difference was found in miscarriage rates.

A Cross-Sectional Comparative Study of Vaginal Microbiota and Spontaneous Abortion at a Tertiary Care Hospital in North Karnataka, India

ObjectiveTo compare the vaginal microbiome in women who have undergone spontaneous abortion with a gestational age of less than 20 weeks to that of women who have a continued pregnancy of the same gestational age. DesignCross-sectional comparative research design. SettingThe study was conducted in a tertiary care hospital of North Karnataka, India. In this rural area, many women lack awareness of prenatal care and women’s health information. Given rising rates of spontaneous abortion, studying the impact of the vaginal microbiome on pregnancy outcomes is crucial for raising local awareness. ParticipantsTwo hundred women; 100 experienced spontaneous abortion within 20 weeks’ gestation, and 100 maintained pregnancy with the same gestational age. MeasuresVaginal swab was used to detect participants’ vaginal microbiota. DNA was extracted from the vaginal samples; the 16S ribosomal RNA sequencing method was used to identify the organisms present. ResultsA pathogen detection rate of 13.15% (n = 200 women) was found in vaginal cultures. The percentages of bacterial detection in women who had spontaneous abortion and those whose pregnancies continued were 19.9% and 7.9%, respectively (p < .05). Compared to women who sustained their pregnancy, women who experienced spontaneous abortion had five common species: Escherichia coli (48%), Enterococcus faecalis (28%), Enterococcus faecium (12%), Pseudomonas fluorescens (7%), and Pseudomonas cedrina (5%); the most prevalent species among those with sustained pregnancy were Lactobacillus iners (58%), Lactobacillus crispatus (32 %), and E. coli (10%; p < .05). ConclusionThe vaginal microbiomes of women with spontaneous abortion were more varied and irregularly distributed with bacteria. The bacteria identified could affect a woman’s pregnancy outcome and perhaps be associated with spontaneous abortion. It is vital for nurses to provide education to women who are in the fertile period regarding prenatal screening, sexually transmitted infections, and perineal care.

Experiences of antenatal care practices to reduce stillbirth: surveys of women and healthcare professionals pre-post implementation of the Safer Baby Bundle

BackgroundThe Safer Baby Bundle (SBB) aimed to reduce stillbirth rates in Australia through improving pregnancy care across five elements; smoking cessation, fetal growth restriction (FGR), decreased fetal movements (DFM), side sleeping in late pregnancy and decision making around timing of birth. We assessed experiences of women and healthcare professionals (HCPs) with antenatal care practices around the five elements.MethodsA pre-post study design using online surveys was employed to assess change in HCPs awareness, knowledge, and frequency of performing recommended practices (22 in total) and women’s experiences of care received related to reducing their chance of stillbirth. Women who had received antenatal care and HCPs (midwives and doctors) at services participating in the SBB implementation program in two Australian states were invited to participate. Surveys were distributed over January to July 2020 (pre) and August to December 2022 (post). Comparison of pre-post responses was undertaken using Fisher’s exact, Pearson’s chi-squared or Wilcoxon rank-sum tests.Results1,225 women (pre-1096/post-129) and 1,415 HCPs (pre-1148/post-267, ≥ 83% midwives) completed the surveys. The frequency of HCPs performing best practice ‘all the time’ significantly improved post-SBB implementation across all elements including providing advice to women on side sleeping (20.4–79.4%, p < 0.001) and benefits of smoking cessation (54.5–74.5%, p < 0.001), provision of DFM brochure (43.2–85.1%, p < 0.001), risk assessments for FGR (59.2–84.1%, p < 0.001) and stillbirth (44.5–73.2%, p < 0.001). Practices around smoking cessation in general showed less improvement e.g. using the ‘Ask, Advise and Help’ brief advice model at each visit (15.6–20.3%, p = 0.088). Post-implementation more women recalled conversations about stillbirth and risk reduction (32.2–50.4%, p < 0.001) and most HCPs reported including these conversations in their routine care (35.1–83.0%, p < 0.001). Most HCPs agreed that the SBB had become part of their routine practice (85.0%).ConclusionsImplementation of the SBB was associated with improvements in practice across all targeted elements of care in stillbirth prevention including conversations with women around stillbirth risk reduction. Further consideration is needed around strategies to increase uptake of practices that were more resistant to change such as smoking cessation support.Trial registrationThe Safer Baby Bundle Study was retrospectively registered on the Australian New Zealand Clinical Trials Registry database, ACTRN12619001777189, date assigned 16/12/2019.

Fetal, neonatal, and infant death among offspring of pregnant women with HIV in Tanzania.

Assess the risk of death for offspring of pregnant women with HIV (PWHIV) and the association with sociodemographic, pregnancy, HIV-related, and birth factors. We conducted a prospective cohort study of PWHIV on antiretroviral therapy (ART) and their offspring in urban Tanzania who were enrolled in a vitamin D trial conducted from June 2015 to October 2019. We described rates of fetal, neonatal, and infant death and assessed risk factors for these outcomes with generalized estimating equations. We also estimated population-attributable risk percentages for the contribution of prematurity and small-for-gestational age (SGA) to neonatal and infant mortality. Among 2299 PWHIV, there were a total of 136 fetal deaths (5.6%) and the stillbirth rate was 42.0 per 1000 total births. Among 2167 livebirths, there were 57 neonatal deaths (26.3 per 1000 livebirths) and 114 infant deaths (52.6 per 1000 livebirths). Twin birth was associated with neonatal death, while maternal CD4 + T-cell count <350 cells/μl in pregnancy was associated with infant death ( P -values < 0.05). As compared to term-appropriate-for-gestational age (AGA) births, the relative risks for neonatal mortality for term-SGA, preterm-AGA, and preterm-SGA infants were 2.07 [95% confidence interval (CI): 1.00-4.28], 2.87 (95% CI 1.54-5.35), and 7.15 (95% CI: 2.11-24.30), respectively. We estimated that 42.7% of neonatal and 29.4% of infant deaths were attributable to prematurity and SGA in the cohort. The risk of death is high for offspring of PWHIV in Tanzania and the combination of prematurity and fetal growth restriction may account for nearly half of neonatal deaths.

Ovulation-induced frozen embryo transfer regimens in women with polycystic ovary syndrome: a systematic review and meta-analysis.

To evaluate whether the type of frozen embryo transfer (FET) regimen - ovulation-induced regimens vs. hormone replacement therapy regimens (HRT) - is associated with live birth rates and the risk of hypertensive diseases of pregnancy (HDP) in women with polycystic ovary syndrome (PCOS). All studies in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched using a combination of MeSH terms and keywords. Inclusion criteria included studies on women with a diagnosis of PCOS, utilization of FET, and reporting of pregnancy and/or obstetric outcomes. Studies were excluded if they were case series or conference abstracts or used other FET regimens. A random effects meta-analysis was performed. Primary outcomes include relative risk (RR) of live birth and HDP. Eleven studies were included in the meta-analysis for the final review. Ovulation-induced regimens were associated with a higher live birth rate (8 studies, RR 1.14 [95% CI 1.08, 1.21]) compared to HRT regimens. The risk of HDP (3 studies RR 0.78 [95% CI 0.53, 1.15]) was not significantly different. Ovulation-induced regimens were associated with a lower miscarriage rate (9 studies, RR 0.67 [95% CI 0.59-0.76]). Rates of clinical pregnancy (10 studies, RR 1.05 [95% CI 0.99, 1.11]) and ectopic pregnancy (7 studies, RR 1.40 [95% CI 0.84, 2.33]), were not significantly different. This SR/MA demonstrates that for women with PCOS, ovulation-induced FET regimens are associated with higher rates of live birth and lower rates of miscarriage compared to HRT regimens.

Decreased AMPK/SIRT1/PDK4 induced by androgen excess inhibits human endometrial stromal cell decidualization in PCOS

Polycystic ovary syndrome (PCOS) is a complex common endocrine disorder affecting women of reproductive age. Ovulatory dysfunction is recognized as a primary infertile factor, however, even when ovulation is medically induced and restored, PCOS patients continue to experience reduced cumulative pregnancy rates and a higher spontaneous miscarriage rate. Hyperandrogenism, a hallmark feature of PCOS, affects ovarian folliculogenesis, endometrial receptivity, and the establishment and maintenance of pregnancy. Decidualization denotes the transformation that the stromal compart of the endometrium must undergo to accommodate pregnancy, driven by the rising progesterone levels and local cAMP production. However, studies on the impact of hyperandrogenism on decidualization are limited. In this study, we observed that primary endometrial stromal cells from women with PCOS exhibit abnormal responses to progesterone during in vitro decidualization. A high concentration of testosterone inhibits human endometrial stromal cells (HESCs) decidualization. RNA-Seq analysis demonstrated that pyruvate dehydrogenase kinase 4 (PDK4) expression was significantly lower in the endometrium of PCOS patients with hyperandrogenism compared to those without hyperandrogenism. We also characterized that the expression of PDK4 is elevated in the endometrium stroma at the mid-secretory phase. Artificial decidualization could enhance PDK4 expression, while downregulation of PDK4 leads to abnormal decidualization both in vivo and in vitro. Mechanistically, testosterone excess inhibits IGFBP1 and PRL expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. Based on co-immunoprecipitation analysis, we observed an interaction between SIRT1 and PDK4, promoting glycolysis to facilitate decidualization. Restrain of AR activation resumes the AMPK/SIRT1/PDK4 pathway suppressed by testosterone excess, indicating that testosterone primarily acts on decidualization through AR stimulation. Androgen excess in the endometrium inhibits decidualization by disrupting the AMPK/SIRT1/PDK4 signaling pathway. These data demonstrate the critical roles of endometrial PDK4 in regulating decidualization and provide valuable information for understanding the underlying mechanism during decidualization.

Antibiotics improve reproductive outcomes after frozen-thaw embryo transfer for chronic endometritis treatment, especially in those with repeated implantation failure

PurposeTo investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE.MethodsA retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up.ResultsOut of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P < 0.05). Analysis of the effect of CE on pregnancy outcomes in FET cycles after antibiotic treatment indicated that treated CE patients exhibited a significantly lower miscarriage rate (8.7%) and early miscarriage rate (2.9%) than untreated non-CE patients (20.2%, 16.8%). Moreover, the singleton live birth rate (45.5%) was significantly higher in treated CE patients than in untreated non-CE patients (32.7%). Survival analysis revealed a statistically significant difference in the first clinical pregnancy time between treated CE and untreated non-CE patients after hysteroscopy (P = 0.0019). Stratified analysis based on the presence of recurrent implantation failure (RIF) demonstrated that in the RIF group, treated CE patients were more likely to achieve clinical pregnancy than untreated non-CE patients (P = 0.0021). Among hysteroscopy-positive patients, no significant difference was noted in pregnancy outcomes between the treatment and control groups (P > 0.05).ConclusionInfertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF.

The impact of implementing a non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) embryo culture protocol on embryo viability and clinical outcomes.

Are modifications in the embryo culture protocol needed to perform non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) affecting clinical reproductive outcomes, including blastocyst development and pregnancy outcomes? The implementation of an embryo culture protocol to accommodate niPGT-A has no impact on blastocyst viability or pregnancy outcomes. The recent identification of embryo cell-free (cf) DNA in spent blastocyst media has created the possibility of simplifying PGT-A. Concerns, however, have arisen at two levels. First, the representativeness of that cfDNA to the real ploidy status of the embryo. Second, the logistical changes that need to be implemented by the IVF laboratory when performing niPGT-A and their effect on reproductive outcomes. Concordance rates of niPGT-A to invasive PGT-A have gradually improved; however, the impact of culture protocol changes is not as well understood. As part of a trial examining concordance rates of niPGT-A versus invasive PGT-A, the IVF clinics implemented a specific niPGT-A embryo culture protocol. Briefly, this involved initial culture of fertilized oocytes following each laboratory standard routine up to Day 4. On Day 4, embryos were washed and cultured individually in 10 μl of fresh media. On Day 6 or 7, blastocysts were then biopsied, vitrified, and media collected for the niPGT-A analysis. Six IVF clinics from the previously mentioned trial were enrolled in this analysis. In the concordance trial, Clinic A cultured all embryos (97 cycles and 355 embryos) up to Day 6 or 7, whereas in the remaining clinics (B-F) (379 cycles), nearly a quarter of all the blastocysts (231/985: 23.5%) were biopsied on Day 5, with the remaining blastocysts following the niPGT-A protocol (754/985: 76.5%). During the same period (April 2018-December 2020), the IVF clinics also performed standard invasive PGT-A, which involved culture of embryos up to Days 5, 6, or 7 when blastocysts were biopsied and vitrified. In total, 428 (476 cycles) patients were in the niPGT-A study group. Embryos from 1392 patients underwent the standard PGT-A culture protocol and formed the control group. Clinical information was obtained and analyzed from all the patients. Statistical comparisons were performed between the study and the control groups according to the day of biopsy. The mean age, number of oocytes, fertilization rates, and number of blastocysts biopsied were not significantly different for the study and the control group. Regarding the overall pregnancy outcomes, no significant effect was observed on clinical pregnancy rate, miscarriage rate, or ongoing pregnancy rate (≥12 weeks) in the study group compared to the control group when stratified by day of biopsy. The limitations are intrinsic to the retrospective nature of the study, and to the fact that the study was conducted in invasive PGT-A patients and not specifically using niPGT-A cases. This study shows that modifying current IVF laboratory protocols to adopt niPGT-A has no impact on the number of blastocysts available for transfer and overall clinical outcomes of transferred embryos. Whether removal of the invasive biopsy step leads to further improvements in pregnancy rates awaits further studies. This study was funded by Igenomix. C.R., L.N.-S., and D.V. are employees of Igenomix. D.S. was on the Scientific Advisory Board of Igenomix during the study. ClinicalTrials.gov (NCT03520933).

Immunological testing for female infertility: a modern view on the problem

Introduction. According to various estimates, in Russia 10 to 20 % of people of reproductive age are infertile. Changes in the immune system play a key role in the etiology and treatment of various infertility forms. The active introduction of immunological testing into clinical practice can potentially improve the results of infertility diagnostics and treatment.Aim: to analyze the current literature data on immunological testing in female infertility, as well as to assess its potential role in infertility diagnostics and treatment.Materials and Methods. There was conducted a search for publications in the electronic databases PubMed and eLibrary by using the following keywords and their combinations: "infertility", "immunology", "immune system", "immunological testing", "diagnostics", "treatment". The articles were evaluated in accordance with the PRISMA recommendations. Ultimately, 88 publications were included in the review.Results. Testing for antiphospholipid antibodies (APA) may be useful for women undergoing assisted reproductive technology (ART) therapy, as these antibodies increase the risk of pregnancy complications and thrombotic risks associated with ovarian stimulation, but studies assessing AFA effect on in vitro fertilization (IVF) outcomes have ambiguous results. The presence of antithyroid antibodies (ATA) may be associated with infertility, so their assessment is indeed important to determine treatment tactics. It has been suggested that antinuclear antibodies (ANA) may affect reproductive function by disrupting trophoblast cell development and interfering with RNA transcription, which may lead to lowered reproductive success. Studies have shown that patients with a positive ANA data have a lower incidence of pregnancy and a higher rate of miscarriages after IVF procedure. The human herpes virus type 6 (HHV-6) affects female fertility and is often the cause of spontaneous termination of pregnancy. B-cell lymphoma protein 6 (BCL-6) can serve as an important prognostic biomarker to identify individuals with endometriosis and related reproductive disorders, including idiopathic infertility. Evaluation of endometrial decidualization can be a useful tool to assess readiness for endometrial implantation and provide opportunities for targeted therapeutic interventions. The issue of testing for NK-cells in patients undergoing infertility screening remains controversial due to the difficulties of standardizing testing recommendations.Conclusion. To date, there is a limited number of reliable data on the role of various immunological tests in infertility diagnostics and treatment. With the exception of testing for AFA in patients with RPL, as well as for thyroid-stimulating hormone (TSH) and anti-thyroperoxidase antibodies (TPOAb) in patients undergoing therapy using various types of assisted reproductive technologies, the remaining immunological tests provide scant data to justify their routine use in clinical practice. The major limitations of existing studies are coupled to a small patient sample, as well as heterogeneity of inclusion criteria, patient groups and research methods.

Analysis of the Effect of Letrozole Tablets Combined with Menotrophin in the Treatment of Infertility of Polycystic Ovary Syndrome

Objective: To investigate the clinical effects of Letrozole tablets combined with Menotrophin in infertile patients with polycystic ovary syndrome (PCOS). Methods: The time period of the study was from February 2023 to February 2024; 62 cases of PCOS infertility patients admitted to our hospital were selected and divided into an observation group (n = 31) and a control group (n = 31) by using the method of a random drawing of medical record number. The patients in the control group were treated with Letrozole tablets, and the patients in the observation group were treated with Letrozole tablets combined with Menotrophin, and the sex hormone levels, ovulation rate, the number of mature follicles, endometrial thickness, pregnancy rate, and early miscarriage rate were compared between the two groups. Results: Before treatment, the sex hormone levels of the two groups were compared, and there was no statistical difference (P &gt; 0.05). After treatment, the sex hormone levels of the observation group were all better than those of the control group, and the differences were statistically significant (P &lt; 0.05). The ovulation rate of the observation group was higher than that of the observation group, the number of mature follicles was more than that of the control group, and the endometrial thickness was greater than that of the control group, with statistically significant differences (P &lt; 0.05). The pregnancy rate of the observation group was higher than that of the control group, and the rate of preterm delivery was lower than that of the control group, and the difference was statistically significant (P &lt; 0.05). Conclusion: The combined application of Letrozole tablets and Menotrophin can improve the sex hormone level of PCOS infertility patients, promote their ovulation, improve follicular development, restore the thickness of endometrial lining, and increase the pregnancy rate of the patients and reduce the rate of preterm delivery, which is of value for promotion and application.

Clozapine Safety in Pregnancy: A Clinical Study.

Pregnant women with persistent schizophrenia and related disorders may require ongoing antipsychotic treatment, including clozapine. However, the potential risks of using clozapine during pregnancy and the postnatal period remain uncertain. We conducted a nested case-control study using the National Register of Antipsychotic Medication in Pregnancy (NRAMP) database. Our study assessed pregnancy outcomes among Australian women diagnosed with schizophrenia spectrum disorder and treated with clozapine (n = 14) during the first trimester. These women were compared to 2 subgroups: those treated with quetiapine (n = 53) and those not taking any medication (n = 24) during pregnancy. We observed higher rates of miscarriage in the clozapine group compared to the quetiapine and drug-free groups. The clozapine group had a higher early pregnancy body mass index but lower overall pregnancy weight gain than the other groups. The prevalence of gestational diabetes was significantly higher in the clozapine group. The percentage of vaginal delivery was higher in the clozapine group than in the other 2 groups. Neonatal outcomes such as gestational age, and Apgar scores were similar across groups. The birth weight was lower in the clozapine group compared to the other 2 groups. This study suggests that pregnant women taking clozapine and their babies have greater adverse outcomes compared to other groups. Clozapine appears to be associated with a greater risk of miscarriages, maternal gestational diabetes, and lower birth weight. However, the gestational age, Apgar scores, and admission to NICU/SCN were comparable between all groups.