Cytoplasmic sperm injection (ICSI) - A systematic review of the literature.

Background: Progestin-primed ovarian stimulation (PPOS) stimulates ovaries to block the premature surge of luteinizing hormone (LH) by using micronized progesterone or a progestin during the follicular phase instead of the conventional gonadotropin-releasing hormone (GnRH) analogues or GnRH antagonists downregulating LH to obtain multi-follicle engagement. Current work aims to assess the influence of progestogen treatment on ovarian stimulation and the ability to control LH surge, its efficacy and suitability in retrieving oocytes, without affecting the embryo quality and its benefit among infertile women long-term outcomes on children compared to standard stimulation protocols. Materials and Methods: The literature review used the randomized control trials published in the Pubmed database from January 2015 to April 2021. To generate the citation list, the following keywords were used: 'progestin-primed ovarian stimulation', 'PPOS', 'micronized progesterone', 'medroxyprogesterone', and/or 'dydrogesterone'. The selected articles analyzed the cohort, intervention, and scheme of the progestin-primed ovarian stimulation protocol in controlled ovarian stimulation (COS) for in-vitro fertilization (IVF)/intra cytoplasmic sperm injection (ICSI) used in Assisted Reproductive Technologies (ART). Results: Overall we concluded that PPOS for IVF/ICSI in ART results in a higher number of obtained embryos, lower incidence of OHSS, equal duration of stimulation, number of retrieved oocytes, and number of MII oocytes. It is also suggested that long-term safety in children shows no significant difference between the study and control groups. Conclusions: Despite the outcomes of progestin stimulation cycles among all cohorts, we concluded that poor ovarian responders, patients with PCOS, women of advanced age and oocyte donors benefit the most from using PPOS.

Pediatric antiphospholipid syndrome: is it the same as an adult?

IMPORTANCE: Antiphospholipid syndrome in neonates and children is a rare, but in some cases life-threatening condition with arterial and/or venous thrombosis and/or non-thrombotic neurological, skin, ophthalmological and other manifestations. OBSERVATIONS: This review highlights the available information about the features of pediatric APS, including the rare catastrophic form, the differences between pediatric and adult APS, and the role of genetic thrombophilia in APS manifestation. CONCLUSIONS AND RELEVANCE: The clinical manifestations and treatment options for APS in children may differ from those in adults, and prescribing therapy can be challenging due to the unique clinical and morphological characteristics of the pediatric patient. Pediatric APS may be a predictor of the development of certain autoimmune diseases and classic manifestations of APS in adulthood, therefore, a revision of the existing criteria for the diagnosis and treatment of APS in children is necessary.

The microbiome in pregnancy and early life-Highlights from the 11th Maria Delivoria-Papadopoulos Perinatal Symposium.

This review was based on a symposium that examined novel aspects of the microbiome during pregnancy and early life and explored papers published by the lecturers. For example, it showed that bacterial extracellular vesicles derived from the microbiome harboured in various maternal niches, carried bacterial deoxyribonucleic acid, were isolated from the placenta and may have confounded placental microbiome studies. Maternal diet was responsible for the composition and diversity of breast milk microbiota, and may have shaped the offspring's microbiome and influenced their immune components. Probiotics and antibiotics administered perinatally may have had beneficial but also long-lasting adverse effects on offspring.

Can we improve the outcome of pregnancies with low serum PAPP-A in the first trimester?

OBJECTIVE: This study aimed to assess the impact of micronized progesterone (VMP4) supplementation on pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) multiples of the median (MoM) values during first-trimester screening. METHODS: Out of 8933 patients evaluated, 116 pregnant women with low PAPP-A concentrations in their blood and no fetal chromosomal anomalies (CAs) were included. Three groups were formed: group 1 received VMP4 from 11 to 16 weeks (29 women, 25%), group 2 received VMP4 from 11 to 36 weeks (25 women, 21.5%), and group 3 (62 women, 53.5%) served as controls without receiving progesterone. RESULTS: Results indicated that group 3 had higher rates of complications, including miscarriages (16.37%), preterm delivery (17.8%), and fetal developmental abnormalities (19.4%). Birthweight variations were elevated in pregnancies without progesterone, contrasting with lower variations in VMP4 groups. Group 2, receiving VMP4 until 36 weeks, reported the lowest incidence of abortion and preterm birth (PB), along with the highest mean birth weight. CONCLUSIONS: The conclusion suggests that 200 mg per day of VMP4 up to 36 weeks of supplementation led to fewer placental-related complications in women with very low PAPP-A at first-trimester screening (0.399 MoM). By reporting lower rates of miscarriages, PBs, and fetal developmental abnormalities in the micronized progesterone-treated groups, the study suggests a potential reduction in complications.

Knots of the umbilical cord: Incidence, diagnosis, and management.

Knot(s) of the umbilical cord have received emphasis because the clinical assessments and sonographic literature show a crucial role in fetal outcomes. The true umbilical cord knot could be a knot in a singleton pregnancy or an entanglement of two umbilical cords in monoamniotic twins. Clinical manifestations are almost silent, which can raise clinical challenges. They worsen outcomes, and the pathology can be easily missed during prenatal visits because ultrasonographers do not pay attention to the cord during an obstetric ultrasound scan. However, most medical centers now have ultrasound machines that improve fetal assessment. The umbilical cord should be routinely evaluated during a fetal assessment, and suspicion of an umbilical cord knot can be more frequently diagnosed and is detected only incidentally. Clinical outcome is usually good but depends on the knot's characteristics and if it is tight or loose. In this review, we discuss pathophysiology, the theories on formation, the main risk factors, ultrasound signs and findings, different opinions in the management, and features of pregnancy outcomes feature.

A new technique to preserve the uterus in patients with placenta accreta spectrum disorders.

BACKGROUND: Placenta accreta spectrum disorders are associated with substantial maternal morbidity and mortality. Despite a preoperative diagnosis, the rate of complications remains high, and the condition is generally associated with the need for a hysterectomy. OBJECTIVE: This study aimed to evaluate the outcomes of a new uterine-preserving technique (called the combined approach, including surgical hemostasis, bilateral ligation of the descending branches of the uterine arteries, and hemostatic external supraplacental stitch with the use of the Zhukovsky double-balloon tamponade in patients with placenta accreta spectrum disorders) during cesarean delivery in women with placenta accreta spectrum disorders vs the surgical technique used until 2014. STUDY DESIGN: This retrospective cohort study included 147 patients with placenta accreta spectrum disorders who were divided into 2 groups: the study group (n=95) is to undergo cesarean delivery using the combined approach, and the control group (n=52) is to undergo the surgical technique used until 2014, which included bilateral uterine artery ligation, which is the transfusion of plasma, red blood cells, platelets, and protease inhibitors. RESULTS: The volume of blood loss was 1.5-fold lower (P=.0010), the number of blood transfusions was 5.1-fold lower (P=.026), and the rate of bladder injuries was 19-fold lower (P=.012) in the study group than that in the control group. The duration of hospital stay after delivery was 4 days lesser (P=.001) and the number of hysterectomies was 4.5-fold lower in the study group than in the control group (P=.023). The study groups did not differ in terms of placenta accreta spectrum type. CONCLUSION: The combined approach during cesarean delivery proved to be more effective than the surgical technique used until 2014 in reducing the number of hysterectomies, blood loss volume, number of blood transfusions, and duration of hospital stay in patients with placenta accreta spectrum disorders.

Omega-3 fatty acid supply in pregnancy for risk reduction of preterm and early preterm birth.

This clinical practice guideline on the supply of the omega-3 docosahexaenoic acid and eicosapentaenoic acid in pregnant women for risk reduction of preterm birth and early preterm birth was developed with support from several medical-scientific organizations, and is based on a review of the available strong evidence from randomized clinical trials and a formal consensus process. We concluded the following. Women of childbearing age should obtain a supply of at least 250 mg/d of docosahexaenoic+eicosapentaenoic acid from diet or supplements, and in pregnancy an additional intake of ≥100 to 200 mg/d of docosahexaenoic acid. Pregnant women with a low docosahexaenoic acid intake and/or low docosahexaenoic acid blood levels have an increased risk of preterm birth and early preterm birth. Thus, they should receive a supply of approximately 600 to 1000 mg/d of docosahexaenoic+eicosapentaenoic acid, or docosahexaenoic acid alone, given that this dosage showed significant reduction of preterm birth and early preterm birth in randomized controlled trials. This additional supply should preferably begin in the second trimester of pregnancy (not later than approximately 20 weeks' gestation) and continue until approximately 37 weeks' gestation or until childbirth if before 37 weeks' gestation. Identification of women with inadequate omega-3 supply is achievable by a set of standardized questions on intake. Docosahexaenoic acid measurement from blood is another option to identify women with low status, but further standardization of laboratory methods and appropriate cutoff values is needed. Information on how to achieve an appropriate intake of docosahexaenoic acid or docosahexaenoic+eicosapentaenoic acid for women of childbearing age and pregnant women should be provided to women and their partners.

Events Leading to the Establishment of Pregnancy and Placental Formation: The Need to Fine-Tune the Nomenclature on Pregnancy and Gestation.

Today, there is strong and diversified evidence that in humans at least 50% of early embryos do not proceed beyond the pre-implantation period. This evidence comes from clinical investigations, demography, epidemiology, embryology, immunology, and molecular biology. The purpose of this article is to highlight the steps leading to the establishment of pregnancy and placenta formation. These early events document the existence of a clear distinction between embryonic losses during the first two weeks after conception and those occurring during the subsequent months. This review attempts to highlight the nature of the maternal-embryonic dialogue and the major mechanisms active during the pre-implantation period aimed at "selecting" embryos with the ability to proceed to the formation of the placenta and therefore to the completion of pregnancy. This intense molecular cross-talk between the early embryo and the endometrium starts even before the blastocyst reaches the uterine cavity, substantially initiating and conditioning the process of implantation and the formation of the placenta. Today, several factors involved in this dialogue have been identified, although the best-known and overall, the most important, still remains Chorionic Gonadotrophin, indispensable during the first 8 to 10 weeks after fertilization. In addition, there are other substances acting during the first days following fertilization, the Early Pregnancy Factor, believed to be involved in the suppression of the maternal response, thereby allowing the continued viability of the early embryo. The Pre-Implantation Factor, secreted between 2 and 4 days after fertilization. This linear peptide molecule exhibits a self-protective and antitoxic action, is present in maternal blood as early as 7 days after conception, and is absent in the presence of non-viable embryos. The Embryo-Derived Platelet-activating Factor, produced and released by embryos of all mammalian species studied seems to have a role in the ligand-mediated trophic support of the early embryo. The implantation process is also guided by signals from cells in the decidualized endometrium. Various types of cells are involved, among them epithelial, stromal, and trophoblastic, producing a number of cellular molecules, such as cytokines, chemokines, growth factors, and adhesion molecules. Immune cells are also involved, mainly uterine natural killer cells, macrophages, and T cells. In conclusion, events taking place during the first two weeks after fertilization determine whether pregnancy can proceed and therefore whether placenta's formation can proceed. These events represent the scientific basis for a clear distinction between the first two weeks following fertilization and the rest of gestation. For this reason, we propose that a new nomenclature be adopted specifically separating the two periods. In other words, the period from fertilization and birth should be named "gestation", whereas that from the completion of the process of implantation leading to the formation of the placenta, and birth should be named "pregnancy".

Paid leave to support parenting-A neglected tool to improve societal well-being and prosperity.

Cohesive families and stimulating and caring environments promoting attachment to caregivers is fundamental for a child's physical and psychosocial growth and development. Parental care, supporting early years development, presupposes the presence and involvement of parents in children's daily life with activities that include breastfeeding, playing, reading and storytelling. However, parents have to balance their child's well-being against employment, career progression and gender equality. Universally accessible and equitably available parental leave addresses this challenge. CONCLUSION: Distinct from compulsory maternity leave, leave at full or nearly full pay for both parents benefits not only families but also societal well-being and prosperity.

Nutrition paves the way to environmental toxicants and influences fetal development during pregnancy.

Nutrition plays a major role in the healthy pregnancy and development of the fetus. In addition, nutrition can expose humans to a wide range of potentially hazardous environmental constituents, such as organic pollutants and heavy metals from marine or agricultural food products while processing, producing, and packaging. Humans constantly face these constituents through air, water, soil, food, and domestic products. During pregnancy, the rate of cellular division and differentiation is higher; exposure to any of these environmental toxicants can lead to developmental defects as they cross the placental barrier and, in some cases, can harm the successive generation too, as some contaminants can act on the reproductive cells of the fetus (Diethylstilbestrol). Pregnant women are considered a vulnerable population to food contaminant exposure and require a proper dietary chart and conscious food choices. Food is a source of both essential nutrients and environmental toxicants. Here, we have researched the possible toxicants of the food industry and their influence on the fetus's in-utero development, along with the importance of dietary interventions and the need to balance a healthy diet to overcome the harms. The cumulative exposure to environmental toxicants can influence the mother's prenatal environment and affect the fetus's development.

Management of large paravaginal hematomas with the Zhukovsky vaginal catheter.

OBJECTIVE: To ameliorate the treatment of large paravaginal hematomas postpartum using the Zhukovsky vaginal catheter. METHODS: A retrospective, controlled study including puerperas with large paravaginal hematomas. To assess the effectiveness of the proposed treatment, a group of patients underwent traditional obstetric surgery. A second group of puerperas underwent an integrated approach: the surgical stage (pararectal incision) and the application of the Zhukovsky vaginal catheter. The effectiveness of treatment was assessed according to the following criteria: blood loss volume and hospital admission time. RESULTS: In total, 30 puerperas were included in the study; 15 in each treatment group. Large paravaginal hematomas were reported most often in primiparas (50.0%), in 36.7% were combined with rupture of the vagina and the cervix, and in 10.0% of cases an episiotomy was performed during delivery. In 40.0% of primiparas, the blood loss volume was more than 1000 mL, whereas in multiparous and in multiple pregnancies, blood loss did not exceed 1000 mL (r = -0.49; P = 0.022). In 25.0% of puerperas with a blood loss of up to 1000 mL there were no obstetric injuries; in the group with a blood loss of more than 1000 mL, 83.3% of patients had obstetric injuries. An integrated approach reduced the blood loss volume (r = -0.22; P = 0.29), compared with the traditional surgery, and reduced the hospital admission time from 12 (11.5; 13.5) days to 9 (7.5; 10.0) days (P < 0.001). CONCLUSION: In patients with large paravaginal hematomas treated by an integrated approach we reported a decrease in bleeding, less risk of postoperative complications, and a reduction in the time of the hospital stay.

SARS-CoV-2 Footprints in the Placenta: What We Know after Three Years of the Pandemic.

As the COVID-19 pandemic continues into its third year, there is accumulating evidence on the consequences of maternal infection. Emerging data indicate increased obstetrics risks, including maternal complications, preterm births, impaired intrauterine fetal growth, hypertensive disorders, stillbirth, gestational diabetes, and a risk of developmental defects in neonates. Overall, controversial concerns still exist regarding the potential for vertical transmission. Histopathological examination of the placenta can represent a useful instrument for investigation and can contribute significant information regarding the possible immunohistopathological mechanisms involved in developing unfavorable perinatal outcomes. Based on current evidence, SARS-CoV-2 infection can affect placental tissue by inducing several specific changes. The level of placental involvement is considered one of the determining factors for unfavorable outcomes during pregnancy due to inflammation and vascular injuries contributing to complex cascade immunological and biological events; however, available evidence does not indicate a strong and absolute correlation between maternal infection, placental lesions, and obstetric outcomes. As existing studies are still limited, we further explore the placenta at three different levels, using histology, immunohistochemistry, and molecular genetics to understand the epidemiological and virological changes observed in the ongoing pandemic.

Parental Psychological Distress of Missed Diagnosis of Down Syndrome at Antenatal Screening: A Rare, but Still Real Occurrence - A Case Report and Review of Literature.

INTRODUCTION: Prenatal screening programs are important components for pregnant women care and are often linked with grief and shock based on gestational age or the diagnosis. Lower/no sensitivity is also associated with these screening programs leading to providing false-negative outputs. CASE PRESENTATION: Present work shows a case of missed antenatal diagnosis of Down syndrome and its persistant medical and psychological impact on the family members. We have also discussed the relevant economic and medical-legal issues related to the context and aimed to maintain an adequate awareness among healthcare to discuss properly these investigations (difference between screening and diagnostic testing), their possible outcome (chances of false results) and enabled the pregnant women/couple to take informed decision on early pregnancy. CONCLUSION: These programs are considered as routine clinical practice in many countries from last few years and are necessary to assess the pros and cons of these programs. One of the prime cons involves the likeliness of obtaining a false-negative result due to lack of 100% sensitivity and specificity.

Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome Activation.

In pregnancy, human amniotic fluid extracellular vesicles (HAF-EVs) exert anti-inflammatory effects on T cells and on monocytes, supporting their immunoregulatory roles. The specific mechanisms are still not completely defined. The aim of this study was to investigate the ability of HAF-EVs, isolated from pregnant women who underwent amniocentesis and purified by gradient ultracentrifugation, to affect inflammasome activation in the human monocytes. Proteomic studies revealed that HAF-EV samples expressed several immunoregulatory molecules as well as small amounts of endotoxin. Surprisingly, metagenomic analysis shows the presence of specific bacterial strain variants associated with HAF-EVs as potential sources of the endotoxin. Remarkably, we showed that a single treatment of THP-1 cells with HAF-EVs triggered inflammasome activation, whereas the same treatment followed by LPS and ATP sensitization prevented inflammasome activation, a pathway resembling monocyte refractories. A bioinformatics analysis of microbiota-HAF-EVs functional pathways confirmed the presence of enzymes for endotoxin biosynthesis as well as others associated with immunoregulatory functions. Overall, these data suggest that HAF-EVs could serve as a source of the isolation of a specific microbiota during early pregnancy. Moreover, HAF-EVs could act as a novel system to balance immune training and tolerance by modulating the inflammasome in monocytes or other cells.

European guidelines on perinatal care: corticosteroids for women at risk of preterm birth.

of recommendationsCorticosteroids should be administered to women at a gestational age between 24+0 and 33+6 weeks, when preterm birth is anticipated in the next seven days, as these have been consistently shown to reduce neonatal mortality and morbidity. (Strong-quality evidence; strong recommendation). In selected cases, extension of this period up to 34+6 weeks may be considered (Expert opinion). Optimal benefits are found in infants delivered within 7 days of corticosteroid administration. Even a single-dose administration should be given to women with imminent preterm birth, as this is likely to improve neurodevelopmental outcome (Moderate-quality evidence; conditional recommendation).Either betamethasone (12 mg administered intramuscularly twice, 24-hours apart) or dexamethasone (6 mg administered intramuscularly in four doses, 12-hours apart, or 12 mg administered intramuscularly twice, 24-hours apart), may be used (Moderate-quality evidence; Strong recommendation). Administration of two "all" doses is named a "course of corticosteroids".Administration between 22+0 and 23+6 weeks should be considered when preterm birth is anticipated in the next seven days and active newborn life-support is indicated, taking into account parental wishes. Clear survival benefit has been observed in these cases, but the impact on short-term neurological and respiratory function, as well as long-term neurodevelopmental outcome is still unclear (Low/moderate-quality evidence; Weak recommendation).Administration between 34 + 0 and 34 + 6 weeks should only be offered to a few selected cases (Expert opinion). Administration between 35+0 and 36+6 weeks should be restricted to prospective randomized trials. Current evidence suggests that although corticosteroids reduce the incidence of transient tachypnea of the newborn, they do not affect the incidence of respiratory distress syndrome, and they increase neonatal hypoglycemia. Long-term safety data are lacking (Moderate quality evidence; Conditional recommendation).Administration in pregnancies beyond 37+0 weeks is not indicated, even for scheduled cesarean delivery, as current evidence does not suggest benefit and the long-term effects remain unknown (Low-quality evidence; Conditional recommendation).Administration should be given in twin pregnancies, with the same indication and doses as for singletons. However, existing evidence suggests that it should be reserved for pregnancies at high-risk of delivering within a 7-day interval (Low-quality evidence; Conditional recommendation). Maternal diabetes mellitus is not a contraindication to the use of antenatal corticosteroids (Moderate quality evidence; Strong recommendation).A single repeat course of corticosteroids can be considered in pregnancies at less than 34+0 weeks gestation, if the previous course was completed more than seven days earlier, and there is a renewed risk of imminent delivery (Low-quality evidence; Conditional recommendation).

Valuing maternal, newborn, child and adolescent health for societal progress - Going beyond the economic orthodoxy of gross domestic product.

AIM: In view of the long-standing recognition that gross domestic product (GDP) does not capture the unremunerated work largely conducted by women upon which societal well-being depends, to discuss the implications for GDP of maternal, newborn, child and adolescent health (MNCAH), and its influences on health, well-being and prosperity across the life course and across generations. METHODS: A wide-ranging discussion of the informal think-tank The Venice Forum was held over two days, with inputs from invited experts in person and online. RESULTS: There was consensus that a strong case could be made for inclusion of unremunerated work largely conducted by women as a positive contribution to GDP in view of its impact on future health and prosperity, and conversely exclusion from GDP of outputs from industries which harm health. CONCLUSION: Taken with the current challenges from COVID, climate change and conflict, there is a compelling need to redefine economic progress through equitable models and metrics that incorporate short-/medium-/long-term societal value of activities that improve MNCAH.