Ovarian follicular function is not altered by SARS-CoV-2 infection or BNT162b2 mRNA COVID-19 vaccination.

STUDY QUESTION: Does the immune response to coronavirus disease 2019 (COVID-19) infection or the BNT162b2 mRNA vaccine involve the ovarian follicle, and does it affect its function? SUMMARY ANSWER: We were able to demonstrate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG in follicular fluid (FF) from both infected and vaccinated IVF patients, with no evidence for compromised follicular function. WHAT IS KNOWN ALREADY: No research data are available yet. STUDY DESIGN, SIZE, DURATION: This is a cohort study, composed of 32 consecutive IVF patients, either infected with COVID-19, vaccinated or non-exposed, conducted between 1 February and 10 March 2021 in a single university hospital-based IVF clinic. PARTICIPANTS/MATERIALS, SETTING, METHODS: A consecutive sample of female consenting patients undergoing oocyte retrieval was recruited and assigned to one of the three study groups: recovering from confirmed COVID-19 (n = 9); vaccinated (n = 9); and uninfected, non-vaccinated controls (n = 14). Serum and FF samples were taken and analyzed for anti-COVID IgG as well as estrogen, progesterone and heparan sulfate proteoglycan 2 concentration, as well as the number and maturity of aspirated oocytes and day of trigger estrogen and progesterone measurements. Main outcome measures were follicular function, including steroidogenesis, follicular response to the LH/hCG trigger, and oocyte quality biomarkers. MAIN RESULTS AND THE ROLE OF CHANCE: Both COVID-19 and the vaccine elicited anti-COVID IgG antibodies that were detected in the FF at levels proportional to the IgG serum concentration. No differences between the three groups were detected in any of the surrogate parameters for ovarian follicle quality. LIMITATIONS, REASONS FOR CAUTION: This is a small study, comprising a mixed fertile and infertile population, and its conclusions should be supported and validated by larger studies. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to examine the impact of SARS-Cov-2 infection and COVID-19 vaccination on ovarian function and these early findings suggest no measurable detrimental effect on function of the ovarian follicle. STUDY FUNDING/COMPETING INTEREST(S): The study was funded out of an internal budget. There are no conflicts of interest for any of the authors. TRIAL REGISTRATION NUMBER: CinicalTrials.gov registry number NCT04822012.

Meconium-stained amniotic fluid as a protective factor against childhood dermatitis and skin rash-related hospitalization in the offspring - a population-based cohort analysis.

BACKGROUND: Gut microbiome influences cutaneous diseases including atopic dermatitis. Possible impact of intrauterine exposure to meconium on the occurrence of dermatitis and skin rash was proposed. OBJECTIVE: We investigated the possible influence of intrauterine exposure to meconium-stained amniotic fluid (MSAF) on the occurrence of dermatitis and skin rash-related hospitalizations throughout childhood. METHODS: Singleton deliveries occurring between 1991 and 2014 at a single medical centre were divided into two study groups based on presence or lack of MSAF during delivery. Population-based cohort analysis, Kaplan-Meier survival analysis and Cox proportional hazards model were used to study the association between MSAF and cutaneous morbidity-related hospitalizations. RESULTS: A lower rate of the total dermatitis or skin eruption-related hospitalization was documented in the MSAF-exposed group; 0.78 per 1000-person years (0.9%, n = 312), as compared to 0.98 per 1000-person years in the unexposed group (1.0%, n = 1992) with a hazard ratio of 0.86 (95% CI 0.76-0.96, P = 0.011). The survival curve showed lower cumulative hospitalization rate in the MSAF-exposed group as compared to the unexposed group (log rank P = 0.01). The Cox analysis, controlled for confounders, demonstrated MSAF exposure to be an independent protective factor for dermatitis and skin rash-related hospitalizations during childhood (adjusted HR 0.878 (95% CI 0.779-0.990, P = 0.034). CONCLUSION: Fetal exposure to MSAF appears to be an independent protective factor for dermatitis and skin rash-related hospitalizations in the offspring throughout childhood and adolescence.

Elective cesarean delivery at term and the long-term risk for endocrine and metabolic morbidity of the offspring.

Other than obesity, no definitive insights have been gained regarding the apparent association between mode of delivery and long-term endocrine and metabolic outcomes in the offspring. We aimed to determine whether elective cesarean delivery (CD) impacts on long-term endocrine and metabolic morbidity of the offspring. A population-based cohort analysis was performed including all singleton-term deliveries occurring between 1991 and 2014 at a single tertiary medical center. A comparison was performed between children delivered via a non-emergent CD and those delivered vaginally (VD). Hospitalizations of the offspring up to the age of 18 years involving endocrine morbidity were evaluated. A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence. Cox and a Weibull regression models were used to control for confounders. During the study period 131,880 term deliveries met the inclusion criteria; 8.9% were elective non-urgent CDs (n=11,768) and 91.1% (n=120,112) were VDs. The survival curve demonstrated a significantly higher cumulative incidence of endo-metabolic morbidity in offspring born via CD (P=0.010). In the regression models, adjusted for maternal obesity, CD was not noted as an independent risk factor for long-term pediatric endocrine and metabolic morbidity of the offspring while maternal obesity emerged as a strong predictor. We therefore conclude that CD per-se does not appear to increase the risk for long-term pediatric endo-metabolic morbidity of the offspring.

Preconception counseling: rational, practice and challenges.

Preconception counseling (PCC) is aimed at identifying and modifying risks related to maternal health and pregnancy outcome, prior to pregnancy. The main components of PCC include: maternal risk assessment, maternal education, and initiation of interventions. It is an opportunity to provide essential information regarding pregnancy, possible risks and available management options. At times, PCC provides a unique "time window" for an intervention, prior to the pregnancy, which may reduce maternal and fetal risks. Specific maternal populations may benefit from PCC more than others with regard to optimizing pregnancy outcome. Although PCC has been recommended for years as standard of care, most providers do not offer it and most consumers do not ask for it. The present review discusses the essence of preconception counseling and the evidence for its effectiveness. In addition, specific topics are reviewed in depth including folic acid supplementation, obesity, depression, seizure disorders, and drug therapy during pregnancy.

The transfer of 6-mercaptopurine in the dually perfused human placenta.

The immunosuppressant azathioprine is increasingly being used in pregnancy. The human placenta is considered a relative barrier to the major metabolite, 6-mercaptopurine (6-MP), and likely explains the lack of proven teratogenicity in humans. The aim of this study was to determine how the human placenta restricts 6-MP transfer using the human placental perfusion model. After addition of 50 ng/ml (n=4) and 500 ng/ml (n=3) 6-MP into the maternal circulation, there was a biphasic decline in its concentration and a delay in fetal circulation appearance. Under equilibrative conditions, the fetal-to-maternal concentration ratio was >1.0 as a result of ion trapping. Binding to placental tissue and maternal pharmacokinetic parameters are the main factors that restrict placental transfer of 6-MP. Active transport is unlikely to play a significant role and drug interactions involving, or polymorphisms in, placental drug efflux transporters are not likely to put the fetus at risk of higher 6-MP exposure.

Teratogenicity of angiotensin converting enzyme inhibitors or receptor blockers.

Studies of 1st trimester exposure to ACE inhibitors and angiotensin receptor blockers examining teratogenicity have shown conflicting results. We systematically reviewed the literature and performed a meta-analysis evaluating the risk of major malformations. For the meta-analysis, we included studies comparing 1st trimester exposure to no exposure, or to exposure to other antihypertensives. Additionally, we conducted a qualitative analysis of studies that did not meet the inclusion criteria for the meta-analysis. A significant risk ratio was found when the exposed group was compared with healthy controls but not when compared with other antihypertensives. The qualitative analysis did not demonstrate a specific pattern of major malformations. Our results suggest that 1st trimester exposure to ACE inhibitors and angiotensin receptor blockers is not associated with an elevated risk of major malformations compared with other antihypertensives. A 1st trimester exposure to antihypertensives in general may be associated with an elevated risk of major malformations.

Suspected macrosomia? Better not tell.

OBJECTIVE: To evaluate the management policy of delivery in a suspected macrosomic fetus and to describe the outcome of this policy. STUDY DESIGN: For this prospective observational study we followed the management by reviewing the medical records of 145 women and their infants. The study population included women at term admitted to the obstetrics department with suspected macrosomic infants, as was diagnosed by an obstetrician and/or by fetal sonographic weight estimation of > or =4,000 g. The comparison group (n = 5,943) consisted of all women who gave birth during the data collection period. RESULTS: Induction of labor and cesarean delivery rates in the macrosomic pregnancies (actual birth weight >4,000 g) of the study group were significantly higher when compared with the macrosomic pregnancies of the comparison group. When comparing the non-macrosomic to the macrosomic pregnancies (actual birth weight 4,000 g) of the study group no significant difference was demonstrated regarding maternal or infant complications. The sensitivity, specificity and positive predictive value of the methods used for detecting macrosomia were 21.6, 98.6 and 43.5%, respectively. CONCLUSION: Our ability to predict macrosomia is poor. Our management policy of suspected macrosomic pregnancies raises induction of labor and cesarean delivery rates without improving maternal or fetal outcome.

Rectovaginal septal repair: case presentations and introduction of a modified reconstruction technique.

Rectovaginal fistula are a relatively rare kind of anorectal fistulas. Spontaneous healing is rare and the rectal advancement flap repair is the most popular procedure with success rates ranging between 60% and 80%. We present a new technique for repairing damage in the rectovaginal septum that consists of placing a folded polyglycolic acid mesh (Dexon) between the levator ani muscle closure area and the vaginal wall. This absorbable mesh separates the suture lines on the vaginal and rectal walls, and induces fibrosis and healing. The technique was performed in four women suffering from a rectovaginal fistula due to different causes. It was successful in all cases.

Multiple courses of antenatal steroids: risks and benefits.

OBJECTIVE: To review the existing literature regarding the effect of multiple courses of antenatal corticosteroids in reducing the occurrence of complications arising because of lung immaturity. DATA SOURCES: A systematic review of the English-language literature was conducted using a computerized database. We searched the English-language human and animal literature in MEDLINE and PubMed (National Library of Medicine, Bethesda, MD), as well as abstracts from recent meetings of the Society for Gynecologic Investigation and the Society for Maternal-Fetal Medicine. The search terms used were antenatal steroids, prenatal steroids, and respiratory distress syndrome. STUDY SELECTION: We screened 2472 abstracts and found 280 relevant articles, which we independently reviewed. Only prospective well-designed animal studies were included. In humans, no well-designed randomized controlled trials (RCTs) were identified. Data that specifically addressed the issue of beneficial and adverse outcome of multiple courses of antenatal corticosteroids were included. TABULATION, INTEGRATION, AND RESULTS: Twelve studies and three abstracts concerning animal models were included. These suggest multiple adverse consequences including decrease in birth and lung weights and brain growth restriction. In humans, 14 publications and five abstracts, mostly in the form of retrospective studies, although methodologically lacking, were included. Possible beneficial effects include lower rates of respiratory distress syndrome and a decrease in oxygen use, whereas adverse outcomes embody reduction in birth head circumference, birth weights, and increased neonatal and maternal infection rates. CONCLUSION: To date, there are no well-designed RCTs in humans that support the advantages of multiple courses over a single course of antenatal corticosteroids. An increasing body of evidence raises the concern of adverse consequences from the use of repeated courses. While awaiting results from RCTs in progress, we recommend that a single course of antenatal corticosteroids be given to all women at risk for preterm birth at 24-34 weeks' gestation.

Accidental vaginal incision during cesarean section. A report of four cases.

BACKGROUND: Transverse vaginal incision during cesarean section, also known as anterior vaginotomy, is a recognized entity, mostly made unintentionally. CASES: At our institution, four patients underwent a transverse vaginal incision during cesarean section over an eight-year period. In three of them, excessive bleeding required blood transfusion. In one case, only hypogastric artery ligation resulted in bleeding control. None of the patients had subsequent vaginal deliveries. CONCLUSION: The exact incidence of anterior vaginotomy is difficult to evaluate. Accidental vaginal incision occurs mostly following a prolonged second stage of labor but is possible during the first stage. Risk factors include prolonged second stage of labor and an emergency setup. Reported complications resulting from anterior vaginotomy include excessive hemorrhage, with a possible need for hysterectomy, difficult approximation, and bladder or ureter injury. Massive bleeding and multiple blood transfusions occurred in our series as well. Fetal outcome and future obstetric behavior do not seem to be compromised. A high index of suspicion is essential when trying to avoid accidental anterior vaginotomy. Meticulous hemostasis, a search for bladder injury and anatomic closure are mandatory when managing this complication.