An averaging model for analysis and interpretation of high-order genetic interactions.

While combinatorial genetic data collection from biological systems in which quantitative phenotypes are controlled by active and inactive alleles of multiple genes (multi-gene systems) is becoming common, a standard analysis method for such data has not been established. The currently common approaches have three major drawbacks. First, although it is a long tradition in genetics, modeling the effect of an inactive allele (a null mutant allele) contrasted against that of the active allele (the wild-type allele) is not suitable for mechanistic understanding of multi-gene systems. Second, a commonly-used additive model (ANOVA with interaction) mathematically fails in estimation of interactions among more than two genes when the phenotypic response is not linear. Third, interpretation of higher-order interactions defined by an additive model is not intuitive. I derived an averaging model based on algebraic principles to solve all these problems within the framework of a general linear model. In the averaging model: the effect of the active allele is contrasted against the effect of the inactive allele for easier mechanistic interpretations; there is mathematical stability in estimation of higher-order interactions even when the phenotypic response is not linear; and interpretations of higher-order interactions are intuitive and consistent-interactions are defined as the mean effects of the last active genes added to the system. Thus, the key outcomes of this study are development of the averaging model, which is suitable for analysis of multi-gene systems, and a new, intuitive, and mathematically and interpretationally consistent definition of a genetic interaction, which is central to the averaging model.

Systematic review and meta-analysis on the effect of adjuvant gonadotropin-releasing hormone agonist (GnRH-a) on pregnancy outcomes in women with endometriosis following conservative surgery.

BACKGROUND: Endometriosis frequently results in pain and infertility. While conservative surgery offers some relief, it often falls short of ensuring satisfactory pregnancy outcomes. Adjuvant GnRH-a is administered post-surgery to mitigate recurrence; however, its impact on pregnancy outcomes remains debated. This study endeavors to assess the efficacy of adjuvant GnRH-a in enhancing pregnancy outcomes post-conservative surgery in endometriosis patients. METHODS: Databases including PubMed, Embase, the Cochrane Library, Medline (Ovid), Web of Science, and Scopus were rigorously searched up to 02 August 2023, without linguistic constraints. Identified articles were screened using strict inclusion and exclusion criteria. Evaluated outcomes encompassed pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, multiple pregnancy rate, mean postoperative pregnancy interval, recurrence rate, and adverse reaction rate. The Cochrane risk of bias tool and the Jadad score evaluated the included studies' quality. Subgroup and sensitivity analysis were implemented to analyze the pooled results. A meta-analysis model expressed results as standardized mean difference (SMD) and Risk ratio (RR). RESULTS: A total of 17 studies about 2485 patients were assimilated. Meta-analysis revealed that post-surgery, the GnRH-a cohort experienced a marginally elevated pregnancy rate (RR = 1.20, 95% CI = 1.02-1.41; P = 0.03) and a reduced mean time to conceive (RR = -1.17, 95% CI = -1.70- -0.64; P < 0.0001). Contrarily, other evaluated outcomes did not exhibit notable statistical differences. CONCLUSIONS: Incorporating adjuvant GnRH-a following conservative surgery may be deemed beneficial for women with endometriosis, especially before Assisted Reproductive Technology (ART). Nonetheless, owing to pronounced heterogeneity, subsequent research is warranted to substantiate these potential advantages conclusively. REGISTRATION NUMBER: CRD42023448280.

Multifetal Pregnancy After Implementation of a Publicly Funded Fertility Program.

Importance: A publicly funded fertility program was introduced in Ontario, Canada, in 2015 to increase access to fertility treatment. For in vitro fertilization (IVF), the program mandated an elective single-embryo transfer (eSET) policy. However, ovulation induction and intrauterine insemination (OI/IUI)-2 other common forms of fertility treatment-were more difficult to regulate in this manner. Furthermore, prior epidemiologic studies only assessed fetuses at birth and did not account for potential fetal reductions that may have been performed earlier in pregnancy. Objective: To examine the association between fertility treatment and the risk of multifetal pregnancy in a publicly funded fertility program, accounting for both fetal reductions and all live births and stillbirths. Design, Setting, and Participants: This population-based, retrospective cohort study used linked administrative health databases at ICES to examine all births and fetal reductions in Ontario, Canada, from April 1, 2006, to March 31, 2021. Exposure: Mode of conception: (1) unassisted conception, (2) OI/IUI, or (3) IVF. Main Outcomes and Measures: The main outcome was multifetal pregnancy (ie, a twin or higher-order pregnancy). Modified Poisson regression generated adjusted relative risks (ARRs) and derived population attributable fractions (PAFs) for multifetal pregnancies attributable to fertility treatment. Absolute rate differences (ARDs) were used to compare the era before eSET was promoted (2006-2011) with the era after the introduction of the eSET mandate (2016-2021). Results: Of all 1 724 899 pregnancies, 1 670 825 (96.9%) were by unassisted conception (mean [SD] maternal age, 30.6 [5.2] years), 24 395 (1.4%) by OI/IUI (mean [SD] maternal age, 33.1 [4.4] years), and 29 679 (1.7%) by IVF (mean [SD] maternal age, 35.8 [4.7] years). In contrast to unassisted conception, individuals who received OI/IUI or IVF tended to be older, reside in a high-income quintile neighborhood, or have preexisting health conditions. Multifetal pregnancy rates were 1.4% (95% CI, 1.4%-1.4%) for unassisted conception, 10.5% (95% CI, 10.2%-10.9%) after OI/IUI, and 15.5% (95% CI, 15.1%-15.9%) after IVF. Compared with unassisted conception, the ARR of any multifetal pregnancy was 7.0 (95% CI, 6.7-7.3) after OI/IUI and 9.9 (95% CI, 9.6-10.3) after IVF, with corresponding PAFs of 7.1% (95% CI, 7.1%-7.2%) and 13.4% (95% CI, 13.3%-13.4%). Between the eras of 2006 to 2011 and 2016 to 2021, multifetal pregnancy rates decreased from 12.9% to 9.1% with OI/IUI (ARD, -3.8%; 95% CI, -4.2% to -3.4%) and from 29.4% to 7.1% with IVF (ARD, -22.3%; 95% CI, -23.2% to -21.6%). Conclusions and Relevance: In this cohort study of more than 1.7 million pregnancies in Ontario, Canada, a publicly funded IVF program mandating an eSET policy was associated with a reduction in multifetal pregnancy rates. Nevertheless, ongoing strategies are needed to decrease multifetal pregnancy, especially in those undergoing OI/IUI.

Assessing the performance of Moghani crossbred lambs derived from different mating systems with Texel and Booroola sheep.

In our ongoing project, which focuses on the introgression of Booroola/FecB gene and the myostatin (MSTN) gene into purebred Moghani sheep, we assessed the performance of second-generation Moghani crossbreds such as second crossbreds (F2) and initial backcross generation (BC1). These crossbreds were generated through different mating systems, including in-breeding, outcrossing, first paternal backcrossing (PBC1), and first maternal backcrossing (MBC1). Notably, F2 strains exhibited lean tail, woolly fleece and a higher percentage of white coat color compared to BC1. The impact of mating systems and birth types on pre-weaning survival rates was found to be statistically significant (P < 0.0001), with singleton offspring resulting from paternal backcross showing a particularly substantial effect. The F2 crossbred lambs carrying the Booroola gene did not show a statistically significant difference in survivability compared to those carrying the MSTN gene, implying the Booroola prolificacy gene had no significant impact on survival outcomes. However, the occurrence of multiple births had a significant negative impact on lamb survival (P < 0.0001). The PBC1 sheep strains, specifically Texel Tamlet ram strains carrying the MSTN mutation, exhibited superior growth rates compared to others (P < 0.05). Interestingly, the MSTN mutation in the homozygous variant genotype significantly impacts growth rate before weaning compared to other genotypes and pure Moghani sheep (P < 0.05). In conclusion, this study objectively underscores the pivotal role of genetic factors, specifically through strategic mating systems like paternal backcrossing, in enhancing desired traits and growth rates in Moghani sheep, thereby contributing valuable insights to the field of sheep breeding programs.

Perinatal and neonatal outcomes of high-risk asymptomatic women from a specialist preterm birth surveillance clinic.

OBJECTIVES: To report the perinatal outcomes of high-risk asymptomatic women who attended a specialist preterm surveillance clinic (PSC) to undergo screening for spontaneous preterm birth (PTB) in Ireland. METHODS: Single center, retrospective cohort study of asymptomatic high risk women who attended the PSC between January 2019 and December 2022. A comprehensive database of all patients who attended the clinic during the study period was constructed and analyzed. Overall outcomes were reported, and stratified per the occurrence of preterm or term birth. Iatrogenic PTBs were included in the outcome data. RESULTS: Following exclusions for loss-to-follow-up, 762 cases were analyzed, constituting 2262 PSC visits. Of those, 183 women were prescribed progesterone (24.0 %), and 100 women underwent cervical cerclage (13.1 %) to prevent spontaneous PTB. Overall, 2.4 %, 6.2 % and 18.6 % of participants gave birth prior to 30 weeks, 34 weeks, and 37 weeks, respectively. The median gestational age at birth for the entire cohort was 38.6 weeks (inter-quartile range (IQR) 37.2-39.6 weeks). Women who delivered < 37 weeks were significantly more likely to be smokers (p = 0.030), have a previous spontaneous PTB (p = 0.016), have multiple pregnancies (p < 0.001), type 1 or 2 diabetes (p = 0.044), or have a previous full dilatation caesarean section birth (p = 0.024). Infants born prior to 37 weeks were more likely to have a lower median birthweight (2270 vs 3300 g, p < 0.001), be admitted to a neonatal intensive care unit (53.8 % vs 2.3 %, p < 0.001) or experience short-term morbidity, including respiratory support (38.0 % vs 1.6 %, p < 0.001). CONCLUSIONS: Over 80% of women deemed to be at high risk of PTB gave birth at term gestations following attendance at a PSC during pregnancy. Most women can be successfully managed without interventions, instead employing a policy of serial cervical surveillance, to identify those at greatest risk of PTB.

Temperature anomalies undermine the health of reproductive-age women in low- and middle-income countries.

Climate change is expected to undermine population health and well-being in low- and middle-income countries, but relatively few analyses have directly examined these effects using individual-level data at global scales, particularly for reproductive-age women. To address this lacuna, we harmonize nationally representative data from the Demographic and Health Surveys on reproductive health, body mass index (BMI), and temporary migration from 2.5 million adult women (ages 15 to 49) in approximately 109,000 sites across 59 low- and middle-income countries, which we link to high-resolution climate data. We use this linked dataset to estimate fixed-effect logistic regression models of demographic and health outcomes as a function of climate exposures, woman-level and site-level characteristics, seasonality, and regional time trends, allowing us to plausibly isolate climate effects from other influences on health and migration. Specifically, we measure the effects of recent exposures to temperature and precipitation anomalies on the likelihood of having a live birth in the past year, desire for another child, use of modern contraception, underweight (BMI < 18.5), and temporary migration, and subsequently allow for nonlinearity as well as heterogeneity across education, rural/urban residence, and baseline climate. This analysis reveals that exposures to high temperatures increase live births, reduce desire for another child, increase underweight, and increase temporary migration, particularly in rural areas. The findings represent clear evidence that anthropogenic temperature increases contribute to temporary migration and are a significant threat to women's health and reproductive autonomy in low- and middle-income countries.

Exploring the lived experiences of women with multiple gestations in Iran: a phenomenological study.

BACKGROUND: Multiple gestations present numerous physical, psychological, social, and economic challenges for women. Understanding the problem-solving experiences of pregnant women carrying multiple can be invaluable. This study aimed to explore the experiences of Iranian women with multiple gestations. METHODS: This descriptive phenomenological study utilized purposive sampling and continued until data saturation. Data collection involved in-depth semi-structured interviews, with analysis performed using Colaizzi's 7-step method. MAXQDA software was employed for data management. RESULTS: This study involved 12 women with multiple gestations. The average age of the participants was 33.76 ± 6.22 years, and 9 were pregnant with triplets. The data were categorized into four primary themes: the paradox of emotions, the pregnancy prison, immersion in fear, and the crystallization of maternal love, encompassing 17 sub-themes. CONCLUSION: Pregnant women with multiple gestations undergo various changes and experience conflicting emotions. Enhancing their ability to adapt to and accept numerous pregnancies can be achieved through supportive, personalized, and family-centered care, along with improvements and revisions in care policies for multiple gestations.

Assessment of artificial intelligence model and manual morphokinetic annotation system as embryo grading methods for successful live birth prediction: a retrospective monocentric study.

PURPOSE: The introduction of the time-lapse monitoring system (TMS) and the development of predictive algorithms could contribute to the optimal embryos selection for transfer. Therefore, the present study aims at investigating the efficiency of KIDScore and iDAScore systems for blastocyst stage embryos in predicting live birth events. METHODS: The present retrospective study was conducted in a private IVF Unit setting throughout a 10-month period from October 2021 to July 2022, and included the analysis of 429 embryos deriving from 91 IVF/ICSI cycles conducted due to infertility of various etiologies. Embryos incubated at the Embryoscope+ timelapse incubator were analyzed through the established scoring systems: KIDScore and iDAScore®. The main outcome measure was the comparison of the two scoring systems in terms of live birth prediction. Embryos with the higher scores at day 5 (KID5 score/iDA5 score) were transferred or cryopreserved for later use. RESULTS: Embryos with high KID5 and iDA5 scores positively correlated with the probability of successful live birth, with KID5 score yielding a higher efficiency in predicting a successful reproductive outcome compared to a proportionally high iDA5 score. KID5 demonstrated conservative performance in successfully predicting live birth compared to iDA5 score, indicating that an efficient prediction can be either provided by a relatively lower KID5 score or a relatively higher iDA5 score. CONCLUSION: The developed artificial intelligence tools should be implemented in clinical practice in conjunction with the conventional morphological assessment for the conduction of optimized embryo transfer in terms of a successful live birth.

Congenital Anomalies in Multiple Pregnancy: A Literature Review.

Importance: Multiple pregnancy is relatively common in many countries and is associated with various pregnancy complications, including preterm birth, low birth weight, and congenital anomalies. In particular, a poorer prognosis has been reported when congenital anomalies overlap with other pregnancy complications in multiple pregnancy compared with singleton pregnancy. Objective: This study reviews the characteristics of congenital anomalies that occur in multiple gestations as compared with singleton pregnancies. Evidence Acquisition: An extensive manual search of major electronic databases was conducted in June 2023. This literature review provides a comprehensive coverage of the congenital anomalies in multiple pregnancy. Results: Most studies have shown that multiple gestations are associated with an increased risk of congenital anomalies compared with singleton pregnancies. In addition, higher rates of congenital anomalies and concordance have been observed in monozygotic versus dizygotic twins. The effect of assisted reproductive therapies on the risk of congenital anomalies appears to be smaller in multiple gestations than in singleton pregnancies. Conclusions: Multiple pregnancy is significantly associated with an increased risk of congenital anomalies. Relevance: This review provides obstetrical providers with the requisite knowledge to offer appropriate antenatal care and prenatal anomaly screening to patients with multiple pregnancies.

Return rate following a live birth obtained with ART: frequency and determinants.

PURPOSE: To understand how often couples return to ART centres for a second child. METHODS: Retrospective monocentric cohort study including women who had a first live birth with IVF. The primary objective was to assess the rate of those returning for a second child within five years of the previous pregnancy. The secondary aim was to disentangle the determinants of this rate. RESULTS: A total of 374 patients were included, of whom 188 returned (50%, 95% CI 45-55%). Among those who did not return (n = 186), four (2%) referred to another ART Center and 24 were unreachable. Of the 158 contacted subjects that did not refer for ART, 53 (34%, 95% CI 27-41%) conceived naturally, 57 (36%, 95% CI 29-44%) abandoned their intent of parenthood, and 48 (30%, 95% CI 24-38%) unsuccessfully attempted natural conception. These 48 women (13%) who expressed interest in a second child but did not undergo ART were compared to those seeking a second pregnancy through ART. Baseline characteristics were similar except for an older age (Median 36, IQR: 34-38 vs 34, IQR: 32-36, p = 0.001). Additionally, in terms of IVF cycle characteristics, women who did not return were more likely to achieve their first pregnancy with a fresh transfer rather than a frozen transfer (75% vs 59%, p = 0.05). They also had a higher number of retrieved oocytes (Median 10, IQR: 7-13 vs 9, IQR: 5-12) and less frequently cryopreserved embryos (27% vs 52%, p = 0.003). CONCLUSION: The proportion of couples who have conceived with ART and who are interested in having a second child is high. Our results underline the importance of paying more attention to the number of intended children, as this information could influence clinical management.

Trend of incompleteness of the Robson Classification variables in the Live Birth Information (SINASC) in the state of Paraná, Brazil, 2014-2020.

OBJECTIVE: To assess the incompleteness of the Robson Classification variables in the Live Birth Information System (Sistema de Informação sobre Nascidos Vivos - SINASC), in the state of Paraná, and its trend, 2014-2020. METHODS: This was a time-series study that analyzed six variables, according to health macro-regions. Incompleteness was classified (percentage of "ignored" and "blank fields") as follows: excellent (< 1.0%); good (1.0-2.9%); regular (3.0-6.9%); poor (≥ 7.0%). Prais-Winsten regression was used to estimate trends. RESULTS: A total of 1,089,116 births were evaluated. The variable "cesarean section before the onset of labor" was classified as poor in 2014 (39.4%) and 2015 (44.3%) in the state and in all macro-regions, but with a decreasing trend in incompleteness. The variables "gestational age" in the North and Northwest macro-regions, and "parity" and "number of fetuses" in the Northwest macro-region showed an increasing trend. CONCLUSION: Most of the variables evaluated showed low percentages of incompleteness with a decreasing trend, but there is a need to improve the completion of some variables.

Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight.

Children conceived through assisted reproductive technologies (ART) have an elevated risk of lower birthweight, yet the underlying cause remains unclear. Our study explores mitochondrial DNA (mtDNA) variants as contributors to birthweight differences by impacting mitochondrial function during prenatal development. We deep-sequenced the mtDNA of 451 ART and spontaneously conceived (SC) individuals, 157 mother-child pairs and 113 individual oocytes from either natural menstrual cycles or after ovarian stimulation (OS) and find that ART individuals carried a different mtDNA genotype than SC individuals, with more de novo non-synonymous variants. These variants, along with rRNA variants, correlate with lower birthweight percentiles, independent of conception mode. Their higher occurrence in ART individuals stems from de novo mutagenesis associated with maternal aging and OS-induced oocyte cohort size. Future research will establish the long-term health consequences of these changes and how these findings will impact the clinical practice and patient counselling in the future.

Effect of frozen-thawed embryo transfer with a poor-quality embryo and a good-quality embryo on pregnancy and neonatal outcomes.

BACKGROUND: To evaluate the impact of embryo quality and quantity, specifically a poor quality embryo (PQE) in combination with a good quality embryo (GQE), by double embryo transfer (DET) on the live birth rate (LBR) and neonatal outcomes in patients undergoing frozen-thawed embryo transfer (FET) cycles. METHODS: A study on a cohort of women who underwent a total of 1462 frozen-thawed cleavage or blastocyst embryo transfer cycles with autologous oocytes was conducted between January 2018 and December 2021. To compare the outcomes between single embryo transfer (SET) with a GQE and DET with a GQE and a PQE, propensity score matching (PSM) was applied to control for potential confounders, and a generalized estimating equation (GEE) model was used to determine the association between the effect of an additional PQE and the outcomes. Subgroup analysis was also performed for patients stratified by female age. RESULTS: After PS matching, DET-GQE + PQE did not significantly alter the LBR (adjusted odds ratio [OR] 1.421, 95% CI 0.907-2.228) compared with SET-GQE in cleavage-stage embryo transfer but did increase the multiple birth rate (MBR, [OR] 3.917, 95% CI 1.189-12.911). However, in patients who underwent blastocyst-stage embryo transfer, adding a second PQE increased the live birth rate by 7.8% ([OR] 1.477, 95% CI 1.046-2.086) and the multiple birth rate by 19.6% ([OR] 28.355, 95% CI 3.926-204.790), and resulted in adverse neonatal outcomes. For patients who underwent cleavage-stage embryo transfer, transferring a PQE with a GQE led to a significant increase in the MBR ([OR] 4.724, 95% CI 1.121-19.913) in women under 35 years old but not in the LBR ([OR] 1.227, 95% CI 0.719-2.092). The increases in LBR and MBR for DET-GQE + PQE compared with SET-GQE in women older than 35 years were nonsignificant toward. For patients who underwent blastocyst-stage embryo transfer, DET-GQE + PQE had a greater LBR ([OR] 1.803, 95% CI 1.165-2.789), MBR ([OR] 24.185, 95% CI 3.285-178.062) and preterm birth rate (PBR, [OR] 4.092, 95% CI 1.153-14.518) than did SET-GQE in women under 35 years old, while no significant impact on the LBR ([OR] 1.053, 95% CI 0.589-1.884) or MBR (0% vs. 8.3%) was observed in women older than 35 years. CONCLUSIONS: The addition of a PQE has no significant benefit on the LBR but significantly increases the MBR in patients who underwent frozen-thawed cleavage-stage embryo transfer. However, for patients who underwent blastocyst-stage embryo transfer, DET-GQE + PQE resulted in an increase in both the LBR and MBR, which may lead to adverse neonatal outcomes. Thus, the benefits and risks of double blastocyst-stage embryo transfer should be balanced. In patients younger than 35 years, SET-GQE achieved satisfactory LBR either in cleavage-stage embryo transfer or blastocyst-stage embryo transfer, while DET-GQE + PQE resulted in a dramatically increased MBR. Considering the low LBR in women older than 35 years who underwent single cleavage-stage embryo transfer, selective single blastocyst-stage embryo transfer appears to be a more promising approach for reducing the risk of multiple live births and adverse neonatal outcomes.

Association Between Assisted Reproductive Technology and Cerebral Palsy: A Meta-Analysis.

BACKGROUND: Since 1978 many children are born thanks to assisted reproductive technology (ART). However, the long-term effects of these therapies are still not fully known. Our objective is to evaluate the risk of cerebral palsy (CP) after ART compared with that in those spontaneously conceived (SC) and to examine this risk in single, multiple, and preterm births and the evolution of the risk over the years. METHODS: PubMed, Embase, and Web of Science databases were searched until December 2022. Studies were included if they studied CP cases in children born through ART. 16 studies were finally selected. Quality of studies was assessed using Newcastle Ottawa Scale. Pooled OR was estimated by weighting individual OR/RR by the inverse of their variance. A random-effect model was applied. To assess the causes of heterogeneity, we performed meta-regression analyses. RESULTS: A significantly high risk of CP was found (OR = 1.27; 95% CI 1.12 to 1.43) in children born through ART compared with those SC. This risk increased in singletons (OR = 1.48; 95% CI 1.23 to 1.79) but disappeared in multiple (OR = 1.05; 95% CI 0.93 to 1.18) and preterm births (OR = 1.09; 95% CI 0.87 to 1.37). We found a higher risk of CP in children born before the year 2000 (OR = 3.40; 95% CI 2.49 to 4.63). CONCLUSIONS: ARTs slightly increase the risk of CP once the effect of multiple gestation is controlled. Further studies are needed to clarify whether the techniques themselves, fertility problems, or associated maternal comorbidities are responsible for this risk.

Annual numbers of diagnoses and medical expenses for obstetric diseases in Japan: A report from the National Database of Health Insurance Claims.

AIM: The present study aimed to estimate the total numbers of obstetric diseases diagnosed, total amounts of medical expenses claimed for obstetric diseases, their averages per livebirth, and yearly trends in Japan. METHODS: This is a secondary analysis of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) (data from 2015 to 2019). The target population was women of reproductive age (15-49 years old) with diseases in pregnancy, childbirth, and the puerperium, defined by having O codes according to the International Classification of Diseases 10th Revision. We calculated the numbers of obstetric diseases diagnosed, amounts of medical expenses claimed for obstetric diseases marked with the "main injury/disease decision flag," and the totals divided by the annual numbers of livebirths, by year and women's age group. RESULTS: From 2015 to 2019, both the numbers of obstetric diseases diagnosed and amounts of medical expenses claimed for obstetric diseases per livebirth were on an upward trend, whereas the total numbers of obstetric diseases diagnosed were decreased. Women in advanced age groups had a higher number of diagnoses and a higher amount of medical expenses for obstetric diseases per livebirth. "Preterm labour without delivery" had the highest amounts of medical expenses claimed for and the second highest numbers of diagnoses throughout the study period. CONCLUSIONS: This study suggests that pregnant women in Japan would have an increasing number of obstetric complications and necessary medical expenses year by year. Further study is warranted to elucidate these trends and identify possible mitigation measures.

Multifetal pregnancy reductions and selective fetocide in a tertiary referral center - a retrospective cohort study.

OBJECTIVES: Multiple pregnancies involve several complications, most often prematurity, but also higher anomaly rates. Reducing fetuses generally improves pregnancy outcomes. We conducted this study to evaluate the obstetrical and neonatal results after multifetal pregnancy reduction (MFPR) in the largest tertiary hospital in Finland. METHODS: This retrospective cohort study included all MFPR managed in Helsinki University Hospital during a 13 year period (2007-2019). Data on pregnancies, parturients and newborns were collected from patient files. The number of fetuses, chorionicities and amnionicities were defined in first-trimester ultrasound screening. RESULTS: There were 54 MFPR cases included in the final analyses. Most often the reduction was from twins to singletons (n=34, 63 %). Majority of these (25/34, 73.5 %) were due to co-twin anomaly. Triplets (n=16, 29.6 %) were reduced to twins (n=7, 13 %) or singletons (n=9, 16.7 %), quadruplets (n=2, 3.7 %) and quintuplets (n=2, 3.7 %) to twins. Most (33/54, 61.1 %) MFPR procedures were done by 15+0 weeks of gestation. There were six miscarriages after MFPR and one early co-twin miscarriage. In the remaining 47 pregnancies that continued as twins (n=7, 14.9 %) or singletons (n=40, 85.1 %) the liveborn rate was 90 % for one fetus and 71.4 % for two fetuses. CONCLUSIONS: Most MFPR cases were pregnancies with an anomalous co-twin. The whole pregnancy loss risk was 11.1 % after MFPR. The majority (70.6 %) of twins were spontaneous, whereas all quadruplets, quintuplets, and 56.3 % of triplets were assisted reproductive technologies (ART) pregnancies. Careful counselling should be an essential part of obstetrical care in multiple pregnancies, which should be referred to fetomaternal units for MFPR option.

Placentation and complications of ART pregnancy. An update on the different possible etiopathogenic mechanisms involved in the development of obstetric complications.

INTRODUCTION: Infertile couples' percentage is increasing all over the world, especially in Italy, with high number of children born in our country through assisted reproductive techniques (ART). However, pregnancies obtained by ART have increased potential obstetrical risks which could be caused by fetus-placenta unit development, most of all due to placentation's evolution. These can be reassumed into miscarriage, chromosomal abnormalities, preterm delivery, multiple pregnancy, IUGR, placenta previa, abruptio placentae, preeclampsia and hypertensive disorders, postpartum hemorrhage. METHODS: The aim of this article is to evaluate hypothetic mechanism involved in placentation process and in the etiopathology of ART pregnancies disorders, giving an updating overview of different etiopathogenetic pathways and features. On this scenario, we create an updated review about the etiopathogenesis of abnormal placentation in ART pregnancies. RESULTS: Several features and different etiopathogenetic characteristic might impact differently such as advanced maternal age, poor ovarian reserve, oocyte quality and causes of subfertility themselves, and the ART techniques itself, as hormonal medical treatments and laboratory techniques such as gamete and embryo laboratory culture, cryopreservation versus fresh ET, number of embryos transferred. CONCLUSION: To further explore the molecular mechanisms behind placentation in ART pregnancies, further studies are necessary to gain a better understanding of the various aspects involved, particularly those which are not fully comprehended. This could prove beneficial to clinicians in both ART care and obstetric care, as it could help to stratify obstetrical risk and decrease complications in women undergoing ART, as well as perinatal disorders in their children. Correct placentation is essential for a successful pregnancy for both mother and baby.

Maternal and Infant Pathways HUB in NE Ohio: Influence on Birth Outcomes.

INTRODUCTION: This investigation examines the outcomes of the Pathways HUB Community Action, a Maternal and Infant Mortality HUB in NE Ohio. The purpose of a HUB is to provide a one-stop point of contact for primarily minority pregnant women who are low-income and are at high risk for pregnancy complications. As a HUB client, each mother is assigned a community health worker who provides wrap-around support across 20 identified areas of potential need. METHODS: The focus of this evaluation is on the women who were enrolled in the PHCA and gave birth between 2016 and 2020. Pre-existing data was used to examine the association between mother variables and birth outcomes using odds ratio and correlation analysis. RESULTS: Using a within-subjects design, results indicate that there is no significant association between preterm rates for women who have previously experienced one or more preterm deliveries. Likewise, results indicate that there is no significant association on the birth weight of infants of enrolled women who have previously given birth to a low-birth-weight infant. Results indicate that there is a strong significant association between 1st and 2nd-trimester enrollee's dosage of PHCA services and supports and positive birth outcomes. DISCUSSION: These findings suggest that the PHCA is providing needed support and assistance to at-risk pregnant women who are mitigating the likelihood of repeated preterm and low-weight births, therefore lowering the likelihood of infant mortality for their clients in Summit County.

This research is the first known study to investigate the impact of HUB services in reducing infant mortality. Since preterm births are the greatest predictor of infant mortality, reducing the number of preterm births can result in better outcomes. Prior preterm births, for those women receiving support from the PHCA, is not longer a significant predictor of another preterm birth.

Trends in preterm birth in the Netherlands in 2011-2019: A population-based study among singletons and multiples.

INTRODUCTION: Preterm birth (PTB) is the leading cause of infant mortality and morbidity worldwide. Rates of PTB in the Netherlands are declining, possibly due to the implementation of preventive strategies. In this study we assessed the overall trend in PTB rates in the Netherlands in recent years, and in more detail in specific subgroups to investigate potential groups that require scrutiny in the near future. MATERIAL AND METHODS: Based on the national perinatal registry, we included all pregnancies without severe congenital abnormalities resulting in a birth from 24 to 42 completed weeks of gestation between 2011 and 2019 in the Netherlands. We assessed PTB rates in two different clinical subtypes (spontaneous vs. iatrogenic) and in five gestational age subgroups: 24-27+6 weeks (extreme), 28-31+6 weeks (very), 32-33+6 weeks (moderate, 34-36+6 weeks [late] and, in general, 24-36+6 weeks [overall PTB]). Trend analysis was performed using the Cochran Armitage test. We also compared PTB rates in different subgroups in the first 2 years compared to the last 2 years. Singleton and multiple gestations were analyzed separately. RESULTS: We included 1 447 689 singleton and 23 250 multiple pregnancies in our study. In singletons, we observed a significant decline in PTB from 5.5% to 5.0% (p < 0.0001), mainly due to a decrease in iatrogenic PTBs. When focusing on different gestational age subgroups, there was a decrease in all iatrogenic PTB and in moderate to late spontaneous PTB. However, in spontaneous extreme and very PTB there was an significant increase. When assessing overall PTB risk in different subgroups, the decline was only visible in women with age ≥25 years, nulliparous and primiparous women, women with a medium or high socioeconomic status and hypertensive women. In multiples, the rate of PTB remained fairly stable, from 52.3% in 2011 to 54.1% in 2019 (p = 0.57). CONCLUSIONS: In the Netherlands, between 2011 and 2019, PTB decreased, mainly due to a reduction in late PTB, and more in iatrogenic than in spontaneous PTB. Focus for the near future should be on specific subgroups in which the decline was not visible, such as women with a low socioeconomic status or a young age.