Uterine Balloon Tamponade under Ultrasound Guidance in Women with Postpartum Hemorrhage: A Retrospective Cohort Study.

Background: Postpartum hemorrhage (PPH) represents one of the principal causes of maternal mortality and morbidity worldwide. Uterine balloon tamponade (UBT) is recommended for the treatment of postpartum hemorrhage due to uterine atony in women who do not respond to pharmacological first-line treatment. The success of UBT in bleeding control is related to the correct positioning of the device, since incorrect insertion can be associated with ineffectiveness and requires time-consuming repositioning maneuvers, with a further increase in blood loss. The use of ultrasound (US) during UBT may increase the success rate by preventing wrong positioning. This study aims to demonstrate the role of US guidance during UBT and to assess whether US guidance can ease positioning and reduce insertion times, preventing additional repositioning maneuvers, in comparison with a US check carried out after balloon insertion. Methods: This was a retrospective study including 370 women who underwent vaginal delivery, had PPH caused by uterine atony and required UBT at Sant'Anna Hospital from 2015 to 2019. The exclusion criteria were an abnormal placental site, vaginal or cervical trauma, coagulation defects, uterine anomalies, previous postpartum hemorrhage and previous caesarean section. Included subjects were divided into two groups: the US-guided group (n = 200) underwent Bakri balloon positioning under US guidance, and the non-guided group (n = 170) received a US check only after balloon insertion. The primary outcome was the success rate of the procedure, expressed as the percentage of cases with bleeding control without the need for balloon repositioning; the secondary outcomes were the length of the procedure and some parameters related to blood loss. Results: The success rate was 99% for the US-guided group vs. 86% for the non-guided group. None of the patients required hysterectomy. In the US-guided group with respect to the non-guided group, we observed a significant reduction in blood loss (1100 ± 450 vs. 1500 ± 600 mL; p < 0.001), Δhemoglobin level (1.8 ± 1.1 vs. 2.7 ± 2.0 g/dL, p < 0.001) and time required for the procedure (8 vs. 13 min, p < 0.001). Conclusions: Our data suggest that the use of US guidance for placement of UBT was associated with reduced need for balloon repositioning, lower blood loss, and faster resolution of postpartum hemorrhage.

New Findings in the Multidisciplinary Management of a Fetal Intrapericardial Teratoma: A Case Report.

INTRODUCTION: Fetal intrapericardial teratoma is a rare tumor that can be diagnosed by antenatal ultrasonography early in pregnancy. CASE PRESENTATION: A fetal intrapericardial teratoma was detected on routine ultrasonography in the second trimester of pregnancy. At 31 weeks gestation, a marked increase in tumor size, fetal ascites, and pericardial effusion were observed, indicating that preterm delivery would be inevitable. Corticosteroid prophylaxis (24 mg of betamethasone in two doses of 12 mg 24 h apart) initiated for prophylaxis of respiratory distress syndrome led to a reduction in fetal ascites and pericardial effusion. Betamethasone therapy (4 mg/per day) was continued with the aim to postpone the expected date of delivery. Gestation was extended for more than 2 weeks. At 33 weeks and 5 days gestation, the neonate was delivered by elective cesarean section with ex utero intrapartum treatment and immediately submitted to fetal cardiac surgery. The infant was discharged from the hospital in good health about 4 months later. CONCLUSION: The present report draws attention to improvement in fetal status and extension of gestation achieved with maternal low-dose corticosteroid therapy on antenatal ultrasound finding of fetal ascites and pericardial effusion due to intrapericardial teratoma.

Innovative Strategies for Fertility Preservation in Female Cancer Survivors: New Hope from Artificial Ovary Construction and Stem Cell-Derived Neo-Folliculogenesis.

Recent advances in anticancer treatment have significantly improved the survival rate of young females; unfortunately, in about one third of cancer survivors the risk of ovarian insufficiency and infertility is still quite relevant. As the possibility of becoming a mother after recovery from a juvenile cancer is an important part of the quality of life, several procedures to preserve fertility have been developed: ovarian surgical transposition, induction of ovarian quiescence by gonadotropin-releasing hormone agonists (GnRH-a) treatment, and oocyte and/or ovarian cortical tissue cryopreservation. Ovarian tissue cryostorage and allografting is a valuable technique that applies even to prepubertal girls; however, some patients cannot benefit from it due to the high risk of reintroducing cancer cells during allograft in cases of ovary-metastasizing neoplasias, such as leukemias or NH lymphomas. Innovative techniques are now under investigation, as in the construction of an artificial ovary made of isolated follicles inserted into an artificial matrix scaffold, and the use of stem cells, including ovarian stem cells (OSCs), to obtain neo-folliculogenesis and the development of fertilizable oocytes from the exhausted ovarian tissue. This review synthesizes and discusses these innovative techniques, which potentially represent interesting strategies in oncofertility programs and a new hope for young female cancer survivors.

Hormone Receptors and Epithelial Ovarian Cancer: Recent Advances in Biology and Treatment Options.

Epithelial ovarian cancer (EOC) is a significant cause of cancer-related mortality in women. Despite advances in diagnosis and treatment, EOC remains a challenging disease to manage, and the 5-year survival rate is still poor. The role of hormone receptors (HRs) in EOC carcinogenesis and prognosis has been actively explored; however, the role of hormone therapy (HT) in the treatment of these tumors is not well established. Most available data on HT mainly come from retrospective series and small early clinical trials. Several of these studies suggest that HT may have a role in adjuvant, maintenance therapy, or in the case of recurrent disease, especially for some subtypes of EOC (e.g., low-grade serous EOC). Furthermore, HT has recently been combined with targeted therapies, but most studies evaluating these combinations are still ongoing. The main aim of this review is to provide an overview of the progress made in the last decade to characterize the biological and prognostic role of HRs for EOC and the developments in their therapeutic targeting through HT.

Reproductive and Obstetric Outcomes Following a Natural Cycle vs. Artificial Endometrial Preparation for Frozen-Thawed Embryo Transfer: A Retrospective Cohort Study.

Background: The proportion of frozen embryo transfer cycles has consistently grown in recent decades. Some adverse obstetric outcomes after frozen embryo transfer could possibly be explained by different approaches in endometrial preparation. The aim of the present study was to investigate reproductive and obstetric outcomes after frozen embryo transfer, comparing different endometrial preparation strategies. Methods: This retrospective study included 317 frozen embryo transfer cycles, of which 239 had a natural or modified natural cycle and 78 underwent artificial endometrial preparation. After excluding late abortion and twin pregnancies, the outcomes of 103 pregnancies were analyzed, 75 of which were achieved after a natural cycle/modified natural cycle, and 28 were achieved after an artificial cycle. Results: The overall clinical pregnancy rate/embryo transfer was 39.7%, the miscarriage rate was 10.1%, and the live birth rate/embryo transfer was 32.8%, without significant differences in reproductive outcomes between natural/modified cycle and artificial cycle groups. The risks of pregnancy-induced hypertension and abnormal placental insertion were significantly increased in pregnancies achieved after the artificial preparation of the endometrium (p = 0.0327 and =0.0191, respectively). Conclusions: Our study encourages the use of a natural cycle or modified natural cycle for endometrial preparation for frozen embryo transfer in order to ensure the presence of a corpus luteum able to orchestrate maternal adaptation to pregnancy.

Chronic kidney disease, female infertility, and medically assisted reproduction: a best practice position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology.

Fertility is known to be impaired more frequently in patients with chronic kidney disease than in the general population. A significant proportion of chronic kidney disease patients may therefore need Medically Assisted Reproduction. The paucity of information about medically assisted reproduction for chronic kidney disease patients complicates counselling for both nephrologists and gynaecologists, specifically for patients with advanced chronic kidney disease and those on dialysis or with a transplanted kidney. It is in this context that the Project Group on Kidney and Pregnancy of the Italian Society of Nephrology has drawn up these best practice guidelines, merging a literature review, nephrology expertise and the experience of obstetricians and gynaecologists involved in medically assisted reproduction. Although all medically assisted reproduction techniques can be used for chronic kidney disease patients, caution is warranted. Inducing a twin pregnancy should be avoided; the risk of bleeding, thrombosis and infection should be considered, especially in some categories of patients. In most cases, controlled ovarian stimulation is needed to obtain an adequate number of oocytes for medically assisted reproduction. Women with chronic kidney disease are at high risk of kidney damage in case of severe ovarian hyperstimulation syndrome, and great caution should be exercised so that it is avoided. The higher risks associated with the hypertensive disorders of pregnancy, and the consequent risk of chronic kidney disease progression, should likewise be considered if egg donation is chosen. Oocyte cryopreservation should be considered for patients with autoimmune diseases who need cytotoxic treatment. In summary, medically assisted reproduction is an option for chronic kidney disease patients, but the study group strongly advises extensive personalised counselling with a multidisciplinary healthcare team and close monitoring during the chosen medically assisted reproduction procedure and throughout the subsequent pregnancy.

Quantization: History and problems.

In this work, I explore the concept of quantization as a mapping from classical phase space functions to quantum operators. I discuss the early history of this notion of quantization with emphasis on the works of Schrödinger and Dirac, and how quantization fit into their overall understanding of quantum theory in the 1920's. Dirac, in particular, proposed a quantization map which should satisfy certain properties, including the property that quantum commutators should be related to classical Poisson brackets in a particular way. However, in 1946, Groenewold proved that Dirac's mapping was inconsistent, making the problem of defining a rigorous quantization map more elusive than originally expected. This result, known as the Groenewold-Van Hove theorem, is not often discussed in physics texts, but here I will give an account of the theorem and what it means for potential ``corrections" to Dirac's scheme. Other proposals for quantization have arisen over the years, the first major one being that of Weyl in 1927, which was later developed by many, including Groenewold, and which has since become known as Weyl Quantization in the mathematical literature. Another, known as Geometric Quantization, formulates quantization in differential-geometric terms by appealing to the character of classical phase spaces as symplectic manifolds; this approach began with the work of Souriau, Kostant, and Kirillov in the 1960's. I will describe these proposals for quantization and comment on their relation to Dirac's original program. Along the way, the problem of operator ordering and of quantizing in curvilinear coordinates will be described, since these are natural questions that immediately present themselves when thinking about quantization.

Pregnancy and COVID-19: The Possible Contribution of Vitamin D.

BACKGROUND: Vitamin D deficiency has been associated with the severity of COVID-19. The role of vitamin D in pregnant women with COVID-19 has been poorly investigated to date. The aim of this study was to evaluate the influence of vitamin D in affecting some clinical features in pregnancy between SARS-CoV-2 positive and negative patients. METHODS: Vitamin D pathway related polymorphisms and 25-hydroxyvitamin D levels were quantified in pregnant women followed from the first to the third trimester of pregnancy. Vitamin D deficiency was considered with values ≤ 30 ng/mL. RESULTS: In total, 160 women were enrolled: 23 resulted positive for at least one SARS-CoV-2 related test (molecular swab or antibody tests). Vitamin D-associated polymorphisms were able to affect vitamin D levels in SARS-CoV-2 negative and positive subjects: remarkably, all the VDR TaqICC genotype patients were negative for SARS-CoV-2. In a sub-population (118 patients), vitamin D levels correlated with pregnancy-related factors, such as alpha-fetoprotein levels. Third-trimester vitamin D levels were lower in preterm births compared to full-term pregnancy: this trend was highlighted for SARS-CoV-2 positive patients. CONCLUSIONS: This is the first study demonstrating a role of vitamin D in affecting the clinical characteristics of pregnant women during the COVID-19 era. Further studies in larger and different cohorts of patients are required to confirm these findings.

Effect of rLH Supplementation during Controlled Ovarian Stimulation for IVF: Evidence from a Retrospective Analysis of 1470 Poor/Suboptimal/Normal Responders Receiving Either rFSH plus rLH or rFSH Alone.

We retrospectively studied a real-life population of 1470 women undergoing IVF, with poor/suboptimal/normal ovarian responsiveness to controlled ovarian stimulation (COS), comparing the cumulative live birth rate (cLBR) when COS was performed using rFSH alone or rFSH + rLH in a 2:1 ratio. Overall, we observed significantly higher cLBR in the rFSH alone group than in the rFSH + rLH group (29.3% vs. 22.2%, p < 0.01). However, considering only suboptimal/poor responders (n = 309), we observed comparable cLBR (15.6% vs. 15.2%, p = 0.95) despite the fact that patients receiving rFSH + rLH had significantly higher ages and worse ovarian reserve markers. The equivalent effectiveness of rFSH + rLH and rFSH alone was further confirmed after stratification according to the number of oocytes retrieved: despite basal characteristics were still in favor of rFSH alone group, the cLBR always resulted comparable. Even subdividing patients according to the POSEIDON classification, irrespective of differences in the baseline clinical characteristics in favor of FSH alone group, the cLBR resulted comparable in all subgroups. Despite the retrospective, real-life analysis, our data suggest that rLH supplementation in COS may represent a reasonable option for patients with predictable or unexpected poor/suboptimal ovarian responsiveness to FSH, those matching the Bologna criteria for poor responsiveness, and those included in the POSEIDON classification.

Increased Placental Anti-Oxidant Response in Asymptomatic and Symptomatic COVID-19 Third-Trimester Pregnancies.

Despite Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) -induced Oxidative Stress (OxS) being well documented in different organs, the molecular pathways underlying placental OxS in late-pregnancy women with SARS-CoV-2 infection are poorly understood. Herein, we performed an observational study to determine whether placentae of women testing positive for SARS-CoV-2 during the third trimester of pregnancy showed redox-related alterations involving Catalase (CAT) and Superoxide Dismutase (SOD) antioxidant enzymes as well as placenta morphological anomalies relative to a cohort of healthy pregnant women. Next, we evaluated if placental redox-related alterations and mitochondria pathological changes were correlated with the presence of maternal symptoms. We observed ultrastructural alterations of placental mitochondria accompanied by increased levels of oxidative stress markers Thiobarbituric Acid Reactive Substances (TBARS) and Hypoxia Inducible Factor-1 α (HIF-1α) in SARS-CoV-2 women during the third trimester of pregnancy. Importantly, we found an increase in placental CAT and SOD antioxidant enzymes accompanied by physiological neonatal outcomes. Our findings strongly suggest a placenta-mediated OxS inhibition in response to SARS-CoV-2 infection, thus contrasting the cytotoxic profile caused by Coronavirus Disease 2019 (COVID-19).

A Novel Xeno-Free Method to Isolate Human Endometrial Mesenchymal Stromal Cells (E-MSCs) in Good Manufacturing Practice (GMP) Conditions.

The cyclic regeneration of human endometrium is guaranteed by the proliferative capacity of endometrial mesenchymal stromal cells (E-MSCs). Due to this, the autologous infusion of E-MSCs has been proposed to support endometrial growth in a wide range of gynecological diseases. We aimed to compare two different endometrial sampling methods, surgical curettage and vacuum aspiration biopsy random assay (VABRA), and to validate a novel xeno-free method to culture human E-MSCs. Six E-MSCs cell samples were isolated after mechanical tissue homogenization and cultured using human platelet lysate. E-MSCs were characterized for the colony formation capacity, proliferative potential, and multilineage differentiation. The expression of mesenchymal and stemness markers were tested by FACS analysis and real-time PCR, respectively. Chromosomal alterations were evaluated by karyotype analysis, whereas tumorigenic capacity and invasiveness were tested by soft agar assay. Both endometrial sampling techniques allowed efficient isolation and expansion of E-MSCs using a xeno-free method, preserving their mesenchymal and stemness phenotype, proliferative potential, and limited multi-lineage differentiation ability during the culture. No chromosomal alterations and invasive/tumorigenic capacity were observed. Herein, we report the first evidence of efficient E-MSCs isolation and culture in Good Manufacturing Practice compliance conditions, suggesting VABRA endometrial sampling as alternative to surgical curettage.

Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal Cells.

Endometrial mesenchymal stromal cells (E-MSCs) extensively contribute to the establishment and progression of endometrial ectopic lesions through formation of the stromal vascular tissue, and support to its growth and vascularization. As E-MSCs lack oestrogen receptors, endometriosis eradication cannot be achieved by hormone-based pharmacological approaches. Quinagolide is a non-ergot-derived dopamine receptor 2 agonist reported to display therapeutic effects in in vivo models of endometriosis. In the present study, we isolated E-MSCs from eutopic endometrial tissue and from ovarian and peritoneal endometriotic lesions, and we tested the effect of quinagolide on their proliferation and matrix invasion ability. Moreover, the effect of quinagolide on E-MSC endothelial differentiation was assessed in an endothelial co-culture model of angiogenesis. E-MSC lines expressed dopamine receptor 2, with higher expression in ectopic than eutopic ones. Quinagolide inhibited the invasive properties of E-MSCs, but not their proliferation, and limited their endothelial differentiation. The abrogation of the observed effects by spiperone, a dopamine receptor antagonist, confirmed specific dopamine receptor activation. At variance, no involvement of VEGFR2 inhibition was observed. Moreover, dopamine receptor 2 activation led to downregulation of AKT and its phosphorylation. Of interest, several effects were more prominent on ectopic E-MSCs with respect to eutopic lines. Together with the reported effects on endometrial and endothelial cells, the observed inhibition of E-MSCs may increase the rationale for quinagolide in endometriosis treatment.

Women in Advanced Reproductive Age: Are the Follicular Output Rate, the Follicle-Oocyte Index and the Ovarian Sensitivity Index Predictors of Live Birth in an IVF Cycle?

(1) Background: Several researchers have investigated alternative markers related to ovarian responsiveness in order to better predict IVF outcomes, particularly in advanced reproductive-aged women. The follicular output rate (FORT), the follicle-oocyte index (FOI) and the ovarian sensitivity index (OSI) are among the most promising. However, these three metrics have not been investigated as independent predictors of live birth in women of advanced reproductive age; neither have they been compared to the two 'component' characteristics that are used to calculate them. (2) Methods: A logistic regression model containing all relevant predictors of ovarian reserve or response was used to evaluate the potential of FORT, FOI and OSI as predictors of live birth. After, the non-linear associations between FORT, FOI and OSI and the probability of live birth were evaluated. Finally, we fitted multiple logistic regression models to compare whether FORT, FOI and OSI were more informative predictors than their components. (3) Results: 590 couples received a total of 740 IVF cycles, after which, 127 (17.5%) obtained a live birth. None of FORT, FOI and OSI showed a strength of association or a p-value even close to female age (odds ratio for live birth (95% confidence interval) 1.00 (0.99-1.01), 1.00 (0.99-1.01), 0.98 (0.88-1.11) and 0.58 (0.48-0.72), respectively). The three models comparing FORT, FOI and OSI with the number of oocytes retrieved, the AFC, the number of preovulatory follicles and the FSH total dose were not more informative. (4) Conclusions: In a population of women of advanced age with unexplained infertility, none of FORT, FOI and OSI were predictive of live birth or more predictive than the two 'component' characteristics that were used to calculate them. We suggest clinicians and researchers still use female age as the most reliable predictor of an IVF treatment.

Expectant Management Before In vitro Fertilization in Women Aged 39 or Above and Unexplained Infertility Does Not Decrease Live Birth Rates Compared to Immediate Treatment.

Unexplained infertile couples can have further expectant management before starting assisted reproductive treatments. However, ovarian reserve and in vitro fertilization (IVF) outcomes rapidly decline after 39 years or more. It is thus important to clarify whether a waiting policy is also appropriate for women of advanced age. Couples who had access to a waiting list for approximately 1 year before receiving reimbursed public IVF were compared with those paying for access to immediate treatment. To allow for comparisons between these two strategies, we followed up couples who opted to pay for 1 year after the last embryo transfer from their first cycle. We calculated the proportion of live births in both groups and compared these using logistic regression models and a two-sample Z test for equality of proportions. Six hundred thirty-five couples were evaluated. Out of 359 couples in the immediate group, 70 (19.5%) had a live birth of which 11 after natural conception and 59 after IVF. Out of 276 couples in the waiting group, 57 (20.7%) had a live birth of which 37 after natural conception and 20 after IVF. There was no statistically significant difference between the two strategies in terms of the crude cumulative live birth rate (cLBR). The adjusted odds ratio of 0.69 (95%CI:0.39-1.22) did not change this conclusion as our sensitivity analyses. The cLBR for the 'waiting before IVF' and the 'immediate' strategies were similar. Further studies are needed to better characterize couples affected by unexplained infertility in order to individualize treatment strategies.

Obstetric and neonatal outcomes after SARS-CoV-2 infection in the first trimester of pregnancy: A prospective comparative study.

OBJECTIVE(S): This prospective observational cohort study aimed to evaluate whether women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the first trimester of pregnancy are at higher risk of adverse obstetric and neonatal outcomes compared to negative patients. STUDY DESIGN: Seromolecular testing for SARS-CoV-2 was performed at 12, 16, 21 weeks, and at delivery; the cohort was then subdivided into a first-trimester SARS-CoV-2-positive (case) group and a SARS-CoV-2-negative (control) group. The primary outcome was a composite adverse obstetric outcome, defined as the presence of either abortion, preterm delivery, preterm prelabor rupture of membranes, preeclampsia, intrauterine growth restriction, stillbirth; and a composite measure of adverse neonatal events, including either 1- and 5-min Apgar score ≤ 7, neonatal intensive care unit admission and congenital birth defects. Maternal symptoms and antibody titer were secondarily assessed. RESULTS: A total of 17 of 164 women tested positive for SARS-CoV-2 (10.3%) in the first trimester. One SARS-CoV-2-positive patient who gave birth at another hospital was excluded. Composite adverse obstetric outcome was observed in 6.2% (1/16) SARS-CoV-2-positive and 10.5% (11/105) SARS-CoV-2-negative women; composite adverse neonatal outcome in 12.5% (2/16) and 7.6% (8/105), respectively. In the newborns of women who had developed IgG antibodies, the same antibodies were detected in arterial cord blood and the nasopharyngeal swab tested negative for SARS-CoV-2. No maternal pneumonia or hospital admission due to coronavirus disease-19 were recorded. CONCLUSION: Asymptomatic or mildly symptomatic women during the first trimester of pregnancy did not experience significantly more adverse events than SARS-CoV-2-negative women.

Preterm birth is not associated with asymptomatic/mild SARS-CoV-2 infection per se: Pre-pregnancy state is what matters.

Evidence for the real impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on preterm birth is unclear, as available series report composite pregnancy outcomes and/or do not stratify patients according to disease severity. The purpose of the research was to determine the real impact of asymptomatic/mild SARS-CoV-2 infection on preterm birth not due to maternal respiratory failure. This case-control study involved women admitted to Sant Anna Hospital, Turin, for delivery between 20 September 2020 and 9 January 2021. The cumulative incidence of Coronavirus disease-19 was compared between preterm birth (case group, n = 102) and full-term delivery (control group, n = 127). Only women with spontaneous or medically-indicated preterm birth because of placental vascular malperfusion (pregnancy-related hypertension and its complications) were included. Current or past SARS-CoV-2 infection was determined by nasopharyngeal swab testing and detection of IgM/IgG antibodies in blood samples. A significant difference in the cumulative incidence of Coronavirus disease-19 between the case (21/102, 20.5%) and the control group (32/127, 25.1%) (P= 0.50) was not observed, although the case group was burdened by a higher prevalence of three known risk factors (body mass index > 24.9, asthma, chronic hypertension) for severe Coronavirus disease-19. Logistic regression analysis showed that asymptomatic/mild SARS-CoV-2 infection was not an independent predictor of spontaneous and medically-indicated preterm birth due to pregnancy-related hypertension and its complications (0.77; 95% confidence interval, 0.41-1.43). Pregnant patients without comorbidities need to be reassured that asymptomatic/mild SARS-CoV-2 infection does not increase the risk of preterm delivery. Preterm birth and severe Coronavirus disease-19 share common risk factors (i.e., body mass index > 24.9, asthma, chronic hypertension), which may explain the high rate of indicated preterm birth due to maternal conditions reported in the literature.

The Gender Gap in the Diagnostic-Therapeutic Journey of the Infertile Couple.

Medical procreation impairs both the biological and psychological lives of couples. However, male and female attitudes to infertility are different and require a different approach during the IVF journey. Thus, the gender impact assessment (GIA) method was used to analyse original studies present in the literature. We found some gender-related differences and, subsequently, possible outcomes of intervention to improve healthy reproduction management and prevent infertility. In particular, it became apparent that there was the need for an in-depth male infertility assessment and a gender-specific follow-up.

Placenta histopathology in SARS-CoV-2 infection: analysis of a consecutive series and comparison with control cohorts.

Infection by SARS-CoV-2 has been shown to involve a wide range of organs and tissues, leading to a kaleidoscope of clinical conditions. Within this spectrum, an involvement of the fetal-maternal unit could be expected, but, so far, the histopathological evaluation of placentas delivered by women with SARS-CoV-2 infection did not show distinct hallmarks. A consecutive series of 11 placentas, delivered by 10 women with COVID-19 admitted to our Obstetrics and Gynecology clinic have been investigated and compared to a control cohort of 58 pre-COVID-19 placentas and 28 placentas delivered by women who had a previous cesarean section. Four out of eleven placentas showed changes consistent with chronic villitis/villitis of unknown etiology (VUE), while in one case, chronic histiocytic intervillositis was diagnosed. Thrombo-hemorrhagic alterations were observed in a subset of cases. Compared to the control cohort, chronic villitis/VUE (p < 0.001), chronic deciduitis (p = 0.023), microvascular thrombosis (p = 0.003), presence of infarction areas (p = 0.047) and of accelerated villous maturation (p = 0.005) showed higher frequencies in placentas delivered by women with COVID-19. Chronic villitis/VUE (p = 0.003) and accelerated villous maturation (p = 0.019) remained statistically significant by restricting the analysis to placentas delivered after a previous cesarean section. The observed differences in terms of pathological findings could be consistent with SARS-CoV-2 pathogenesis, but just a subset of alterations remained statistically significant after adjusting for a previous cesarean section. A careful consideration of potential confounders is warranted in future studies exploring the relationship between COVID-19 and pregnancy.

Luteal Support with very Low Daily Dose of Human Chorionic Gonadotropin after Fresh Embryo Transfer as an Alternative to Cycle Segmentation for High Responders Patients Undergoing Gonadotropin-Releasing Hormone Agonist-Triggered IVF.

The segmentation of the in vitro fertilization (IVF) cycle, consisting of the freezing of all embryos and the postponement of embryo transfer (ET), has become popular in recent years, with the main purpose of preventing ovarian hyperstimulation syndrome (OHSS) in patients with high response to controlled ovarian stimulation (COS). Indeed cycle segmentation (CS), especially when coupled to a GnRH-agonist trigger, was shown to reduce the incidence of OHSS in high-risk patients. However, CS increases the economic costs and the work amount for IVF laboratories. An alternative strategy is to perform a fresh ET in association with intensive luteal phase pharmacological support, able to overcome the negative effects of the GnRH-agonist trigger on the luteal phase and on endometrial receptivity. In order to compare these two strategies, we performed a retrospective, real-life cohort study including 240 non-polycystic ovarian syndrome (PCO) women with expected high responsiveness to COS (AMH >2.5 ng/mL), who received either fresh ET plus 100 IU daily human chorionic gonadotropin (hCG) as luteal support (FRESH group, n = 133), or cycle segmentation with freezing of all embryos and postponed ET (CS group, n = 107). The primary outcomes were: implantation rate (IR), live birth rate (LBR) after the first ET, and incidence of OHSS. Overall, significantly higher IR and LBR were observed in the CS group than in the FRESH group (42.9% vs. 27.8%, p < 0.05 and 32.7% vs. 19.5%, p < 0.05, respectively); the superiority of CS strategy was particularly evident when 16-19 oocytes were retrieved (LBR 42.2% vs. 9.5%, p = 0.01). Mild OHSS appeared with the same incidence in the two groups, whereas moderate and severe OHSS forms were observed only in the FRESH group (1.5% and 0.8%, respectively). In conclusion, in non-PCO women, high responders submitted to COS with the GnRH-antagonist protocol and GnRH-agonist trigger, CS strategy was associated with higher IR and LBR than the strategy including fresh ET followed by luteal phase support with a low daily hCG dose. CS appears to be advisable, especially when >15 oocytes are retrieved.