Haemorrhoidal disease in pregnancy: results from a self-assessment questionnaire administered by means of a social network.

BACKGROUND: The anal symptoms occurring during pregnancy and post-partum, mainly related to Haemorrhoidal Disease (HD), have been reported with in a wide range of incidence in the literature. Although in many cases the course of the disease is mild and self-limiting, sometimes it is severe enough to affect quality of life. METHODS: Our study has been conducted through a questionnaire administered via social media with the aim of obtaining epidemiologic data on the incidence of the symptoms of HD in an unselected population of pregnant women. In addition, we looked for the presence of those factors notoriously predisposing or associated to HD (constipation, straining on the toilet, low dietary fibres and fluid intake). RESULTS: Out of 133 patients 51% reported symptoms of HD during pregnancy, mainly in the second and third trimester. Constipation, straining on the toilet, low dietary fibres and fluid intake were not significantly related to incidence of HD. Only a previous history of HD was correlated to onset of symptoms of HD in pregnancy and reached a statistical significance (odds ratio = 5.2, p < 0.001). CONCLUSION: Although with the limitations posed by the nature of our retrospective study via a self-assessment interview, our results suggest that the occurrence of HD in pregnancy seems not sustained by the classical risk factors observed in the general population. At the moment, specific therapeutic measures are lacking and treatment relies on empiric suggestions concerning diet, fluid intake, bowel care, local ointment. Further studies are needed in order to identify a targeted etiologic treatment.

Ultrasound Features and Clinical Outcome of Patients with Ovarian Masses Diagnosed during Pregnancy: Experience of Single Gynecological Ultrasound Center.

(1) Background: The number of adnexal masses detected during pregnancy has increased due to the use of first-trimester screening and increasingly advanced maternal age. Despite their low risk of malignancy, other risks associated with these masses include torsion, rupture and labor obstruction. Correct diagnosis and management are needed to guarantee both maternal and fetal safety. Adnexal masses may be troublesome to classify during pregnancy due to the increased volume of the uterus and pregnancy-related hormonal changes. Management should be based on ultrasound examination to provide the best treatment. The aim of this study was to describe the ultrasound features of ovarian masses detected during pregnancy and to optimize and personalize their management with the expertise of gynecologists, oncologists and sonographers. (2) Methods: Clinical, ultrasound, histological parameters and type of management (surveillance vs. surgery) were retrospectively retrieved. Patient management, perinatal outcomes and follow-up were also evaluated. (3) Results: according to the literature, these masses are most frequently benign, ultrasound follow-up is the best management, and obstetric outcomes are not considerably influenced by the presence of adnexal masses. (4) Conclusions: the management of patients with ovarian masses detected during pregnancy should be based on ultrasound examination, and a centralization in referral centers for ovarian masses should be considered.

Pre-Eclampsia: From Etiology and Molecular Mechanisms to Clinical Tools-A Review of the Literature.

Pre-eclampsia is a severe pregnancy-related complication that manifests as a syndrome with multisystem involvement and damage. It has significantly grown in frequency during the past 30 years and could be considered as one of the major causes of maternal and fetal morbidity and mortality. However, the specific etiology and molecular mechanisms of pre-eclampsia are still poorly known and could have a variety of causes, such as altered angiogenesis, inflammations, maternal infections, obesity, metabolic disorders, gestational diabetes, and autoimmune diseases. Perhaps the most promising area under investigation is the imbalance of maternal angiogenic factors and its effects on vascular function, though studies in placental oxidative stress and maternal immune response have demonstrated intriguing findings. However, to determine the relative importance of each cause and the impact of actions aiming to significantly reduce the incidence of this illness, more research is needed. Moreover, it is necessary to better understand the etiologies of each subtype of pre-eclampsia as well as the pathophysiology of other major obstetrical syndromes to identify a clinical tool able to recognize patients at risk of pre-eclampsia early.

Perinatal mental illness and autoimmune diseases: a qualitative sistematic review.

INTRODUCTION: The term "perinatal mental illness" refers to the set of psychiatric disorders that occur during pregnancy and up to one year after childbirth. The disorders that occurred before pregnancy along with the disorders that emerge during pregnancy or in the postpartum period are all considered perinatal mental illnesses. The causes of prenatal mental illness are still unknown. However, recent studies have shown a major risk in patients with autoimmune diseases (AIDs). EVIDENCE ACQUISITION: We performed a comprehensive search of relevant studies from February 2000 to December 2021 to ensure all possible studies were captured. A systematic search of PubMed databases was conducted. We selected "autoimmune disease" as the search term, combining with "perinatal mental illness," "perinatal depression" or "postpartum anxiety" or "postpartum psychosis" or "bipolar disorder" or "postpartum blues." EVIDENCE SYNTHESIS: The results of our review show that patients with perinatal mental illness have higher risks of subsequent AIDs. In fact, when a woman develops perinatal mental illness, accurate counseling can be employed: on the one hand, the woman should be send to the psychiatrist, on the other hand she has to be informed about the increased risk of a future developement of AID. CONCLUSIONS: As described in the literature, correlation between perinatal mental illness and AID could bring new diagnostic opportunities, relevant for practical decisions. Further studies need to confirm the correlation between perinatal mental illness and AID.

Sex ratio at birth: causes of variation and narrative review of literature.

INTRODUCTION: The human sex ratio at birth (SRB) is the parameter which reflects the relationship between males and females at birth. It is not 50:50, but approximately 0.515 in favor of males. There are many factors that can influence SRB and its variations are not easily demonstrable. EVIDENCE ACQUISITION: Our aim was to investigate the environmental and human agents capable of causing variations in the SRB by providing a narrative review of the scientific literature. EVIDENCE SYNTHESIS: Studies demonstrated that male and female embryos/fetuses' response to stress in different way and the male ones show less resistance. This phenomenon seems to persist for approximately six months after a stressful event, suggesting a purpose of reproductive regulation and protection of the perpetuation of the species. Although the relationship of dependence with parenting decisions, thanks to prenatal diagnosis and assisted fertility techniques is easily understood, it is more complex to correlate its variations with environmental pressures that act through secondary mechanisms. The Covid-19 pandemic, natural catastrophes, terroristic attacks, economic crises are some of the difficulties encountered in recent times. CONCLUSIONS: The impact of all the factors reported is not explained only with a possible a priori determination of sex at conception, but also with secondary effects in the pregnancy outcomes. Thus, the determination of sex appears to be a complex and multifactorial mechanism, besides a matter of genetics. The pandemic and climate changes are the present important opportunities of research for possibly reaching more certain answers.

Carnitines as Mitochondrial Modulators of Oocyte and Embryo Bioenergetics.

Recently, the importance of bioenergetics in the reproductive process has emerged. For its energetic demand, the oocyte relies on numerous mitochondria, whose activity increases during embryo development under a fine regulation to limit ROS production. Healthy oocyte mitochondria require a balance of pyruvate and fatty acid oxidation. Transport of activated fatty acids into mitochondria requires carnitine. In this regard, the interest in the role of carnitines as mitochondrial modulators in oocyte and embryos is increasing. Carnitine pool includes the un-esterified l-carnitine (LC) and carnitine esters, such as acetyl-l-carnitine (ALC) and propionyl-l-carnitine (PLC). In this review, carnitine medium supplementation for counteracting energetic and redox unbalance during in vitro culture and cryopreservation is reported. Although most studies have focused on LC, there is new evidence that the addition of ALC and/or PLC may boost LC effects. Pathways activated by carnitines include antiapoptotic, antiglycative, antioxidant, and antiinflammatory signaling. Nevertheless, the potential of carnitine to improve energetic metabolism and oocyte and embryo competence remains poorly investigated. The importance of carnitine as a mitochondrial modulator may suggest that this molecule may exert a beneficial role in ovarian disfunctions associated with metabolic and mitochondrial alterations, including PCOS and reproductive aging.

A first stage placental site trophoblastic tumor: a case report and review of literature.

Placental site trophoblastic tumor (PSTT) is a very rare form of gestational trophoblastic disease (GTD) that occurs mainly in women who have a history of termination of pregnancy. It has different characteristics from other gestational trophoblastic tumors: it grows slowly, secretes low levels of beta-human chorionic gonadotropin (ß-hCG), with low metastatic potential. We report a case of PSTT of a 32-year-old patient. Seven months after delivery, the patient presented at our Center with persistence of menorrhagia for at least 1 month. A slightly high level of beta-human chorionic gonadotropin (ß-hCG) was observed. TVUS and MRI, an operative hysteroscopy and a laparoscopy were performed. The histological and immunohistochemical findings demonstrated PSTT. Diagnosis of juvenile cystic adenomyoma (JCA) was also added. A total body CT scan was negative for metastases. A total hysterectomy with salpingectomy was performed. We performed a search of relevant studies about PSTT of the last years. A systematic search of Pubmed databases was conducted. Appropriate search terms were constructed by reviewing abstracts, titles and keywords relating to PSTT known to the authors. All articles known to the authors useful to the review were included, comparing with our clinical case. Stages and treatment are related to survival rates, with long term survival expected for stage I low-risk disease after hysterectomy. Our case is a stage I disease with good prognostic factors (patient's age and absence of metastases) and, as described in the literature, a total hysterectomy with salpingectomy was performed.

Second stimulation in the same ovarian cycle: an option to fully-personalize the treatment in poor prognosis patients undergoing PGT-A.

PURPOSE: Our primary objective was to assess whether immediately undergoing a second stimulation in the same ovarian cycle (DuoStim) for advanced-maternal-age and/or poor-ovarian-reserve (AMA/POR) patients obtaining ≤ 3 blastocysts for preimplantation-genetic-testing-for-aneuploidies (PGT-A) is more efficient than the conventional-approach. METHODS: All AMA/POR patients obtaining ≤ 3 blastocysts after conventional-stimulation between 2017 and 2019 were proposed DuoStim, and 143 couples accepted (DuoStim-group) and were matched for the main confounders to 143 couples who did not accept (conventional-group). GnRH-antagonist protocol with recombinant-gonadotrophins and agonist trigger, intra-cytoplasmatic-sperm-injection (ICSI) with ejaculated sperm, PGT-A and vitrified-warmed euploid single-blastocyst-transfer(s) were performed. The primary outcome was the cumulative-live-birth-delivery-rate per intention-to-treat (CLBdR per ITT) within 1 year. If not delivering, the conventional-group had 1 year to undergo another conventional-stimulation. A cost-effectiveness analysis was also conducted. RESULTS: The CLBdR was 10.5% in the conventional-group after the first attempt. Only 12 of the 128 non-pregnant patients returned (165 ± 95 days later; drop-out = 116/128,90.6%), and 3 delivered. Thus, the 1-year CLBdR was 12.6% (N = 18/143). In the DuoStim-group, the CLBdR was 24.5% (N = 35/143; p = 0.01), 2 women delivered twice and 13 patients have other euploid blastocysts after a LB (0 and 2 in the conventional-group). DuoStim resulted in an incremental-cost-effectiveness-ratio of 23,303€. DuoStim was costlier and more effective in 98.7% of the 1000 pseudo-replicates generated through bootstrapping, and the cost-effectiveness acceptability curves unveiled that DuoStim would be more cost-effective than the conventional-approach at a willingness-to-pay threshold of 23,100€. CONCLUSIONS: During PGT-A treatments in AMA/POR women, DuoStim can be suggested in progress to rescue poor blastocyst yields after conventional-stimulation. It might indeed prevent drop-out or further aging between attempts.

AGEs-related dysfunctions in PCOS: evidence from animal and clinical research.

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder in women in their reproductive age. In recent years, the role of advanced glycation end products (AGEs) in PCOS has gained great attention. AGEs are highly reactive molecules that can be assumed by diet or endogenously synthesized as by-products of metabolic processes. AGE deposition increases with aging, hyperglycemia, insulin resistance, and glycotoxin-rich diet. Therefore, it has become imperative to understand the underlying mechanism of AGEs actions and its downstream effects in PCOS pathophysiology. By integrating evidence from human studies and experimental models, the present review points out that altered AGE deposition is a common feature in all PCOS phenotypes. Searching for possible mechanisms involved in the adaptive response against glycation injury in oocytes and ovaries, the role of SIRT1, the main member of the mammalian sirtuin family, has also recently emerged. Therefore, further studies based on anti-AGE interventions could be helpful in creating innovative strategies for counteracting PCOS and its effects on fertility.

Increased levels of proapoptotic markers in normal ovarian cortex surrounding small endometriotic cysts.

Endometriosis can impair fertility by reducing ovarian reserve and the production of good-quality oocytes. The surgical removal of endometriotic lesions is generally recommended for women who wish to conceive. In this paper we studied whether ovarian cortex adjacent to excised small (diameter ≤ 4 cm) endometriotic cyst (here referred as Cortex Surrounding Endometriotic Cyst, CSEC) showed signs of tissue damages by evaluating the expression of proteins involved in DNA repair and apoptosis. To this end, phosphorylated H2A.X, Chk1 and 2, ATM and ATR, Bcl-2, Bid, phosphorylated and total p53, caspases (9, 8 and 3), XIAP, phosphorylated and total NFκB were analyzed by western blot. Results showed that caspase 8, XIAP, p53/p-p53 and NFκB were more abundantly expressed in all samples of CSEC group in comparison with ovarian cortex of controls. Conversely, the levels of the other proteins were comparable between the two groups. In conclusion, these results suggest that NFκB, caspase 8 and p53/p-p53 elevated expressions in samples of CSEC can be considered as an early sign of tissue injury, indicating that ovarian cortex is already sensitized to apoptosis and inflammation. Therefore, excision of EC should occur very early, to avoid further ovarian damages.

Influence of the Menstrual Cycle Phase on Pain Perception and Analgesic Requirements in Young Women Undergoing Gynecological Laparoscopy.

CONTEXT: The influence of the gonadal hormones on some aspects of the human physiology has been studied with uncertain results. Still a confusion exists in relation to the real effects of the female hormones on the perception of pain. The existing data refer mainly to experimental studies and have provided results not always useful in the clinical practice. DATA SOURCE: This study was designed to detect whether there are differences in the perception of the postoperative pain in women, during two clearly defined phases of hormonal asset: luteal and follicular phases. CONCLUSION: The results of this study have demonstrated that in postoperative female patients pain is perceived significantly more in the luteal phase of the menstrual period, than in the follicular phase. This could suggest that female in child-bearing age should be scheduled for elective surgery preferentially during the follicular phase, unless differently necessary. It would guarantee a more comfortable postoperative period, with reduced necessity of analgesics.

Immunolocalization of Advanced Glycation End Products, Mitogen Activated Protein Kinases, and Transforming Growth Factor-ß/Smads in Pelvic Organ Prolapse.

Collagen and matrix metalloproteinases (MMP) play a pivotal role in the pathophysiology of Pelvic Organ Prolapse (POP) as a switch between type I and III collagen together with a simultaneous activation of MMPs have been observed in the vaginal wall. The aim of this study was to evaluate the Advanced Glycation End (AGE) products, ERK1/2 and transforming growth factor (TGF)-ß/Smad pathway expression in muscularis propria in women with POP compared with control patients. We examined 20 patients with POP and 10 control patients treated for uterine fibromatosis. Immunohistochemical analysis using AGE, RAGE, ERK1/2, Smads-2/3, Smad-7, MMP-3, and collagen I-III, TIMP, and α-SMA were performed. Smad-2/3, Smad-7, AGE, ERK1/2, p-ERK, and p-Smad3 were also evaluated using Western-blot analysis. POP samples from the anterior vaginal wall showed disorganization of the normal muscularis architecture. In POP samples, AGE, ERK1/2, Smad-2/3, MMP-3, and collagen III were upregulated in muscularis whereas in controls, Smad-7 and collagen I were increased. The receptor for AGEs (RAGE) was mild or absent both in controls and prolapse. We demonstrated the involvement of these markers in women with POP but further studies are required to elucidate if the overexpression of these molecules could play a crucial role in the pathophysiology of POP disease.

The effect of voluntary termination of pregnancy on female sexual and emotional well-being in different age groups.

INTRODUCTION: To evaluate the impact of voluntary termination of pregnancy (VTOP) on the psycho-sexological well-being of females before/six months after the abortion. METHODS: A sample of 194 women was recruited from three obstetrics and gynaecological divisions. The women were evaluated for the variables "sexual functioning" with the Female Sexual Function Index (FSFI), "depression" with the Beck Depression Inventory (BDI-II), and "anxiety state" with the Self-Rating Anxiety Scale (SAS) at time 0 (the beginning of the abortion procedure) and time 1 (six months after the abortion). Since 24 women refused to fill out the questionnaires, the final sample was composed of 170 women. RESULTS: The women showed a slight although significant improvement in the mean FSFI score from time 0 (16.7 ± 12.9) to time 1 (20.9 ± 13.8) (p < 0.001) which paralleled with a slight decrease in the incidence of clinically significant sexual dysfunction [49% (84/170) (time 0) versus 34.1% (58/170) (time 1)], (McNemar's test; p = 0.0241). The sub-group of younger women (18-25) showed a lesser increase in FSFI score from time 0 to time 1. In addition, both depression (p = 0.048) and anxiety (p < 0.001) significantly decreased over time. However, the female sexuality remained impaired since more than two thirds (69.5%) of women were sexually dysfunctional six months after VTOP. DISCUSSION: Voluntary TOP may influence the sexuality of younger females differently from how it influences that of older women. Hence, the sexuality of younger female should be regularly supervised in follow-up examinations.

Increased levels of oxidative and carbonyl stress markers in normal ovarian cortex surrounding endometriotic cysts.

Many evidence support the view that endometriotic cyst may exert detrimental effect on the surrounding ovarian microenvironment so representing a risk to functionality of adjacent follicles. Patients with benign ovarian cyst (endometriotic, follicular and dermoid cysts) subjected to laparoscopic cystectomy were enrolled in the present retrospective study in order to analyze whether endometriotic tissue could negatively affect the surrounding normal ovarian cortex more severely than other ovarian cysts. To this end we carried out immunohistochemistry analysis and comparative determination of the transcription factor FOXO3A, oxidized DNA adduct 8-OHdG (8-hydroxy-2'-deoxyguanosine) and damaged proteins known as AGEs (Advanced Glycation End products) as markers of ovarian stress response and molecular damage. Our results show that all the markers analyzed were present in normal ovarian tissue surrounding benign cysts. We observed higher levels of FOXO3A (15.90 ± 0.28), 8-OHdG (13.33 ± 2.07) and AGEs (12.58 ± 4.34) staining in normal ovarian cortex surrounding endometriotic cysts in comparison with follicular cysts (9.04 ± 0.29, 2.67 ± 2.67, 11.31 ± 2.95, respectively) and dermoid cysts (2.02 ± 0.18, 4.33 ± 2.58 and 10.56 ± 4.03, respectively). These results provide evidence that ovarian endometrioma is responsible for more severe alterations to cellular biomolecules than follicular and dermoid cysts.

Post-earthquake birth-rate evaluation using the brief cope.

BACKGROUND: The study arises from the idea of analyzing the reasons why many women in L'Aquila decided to conceive in the months following the 2009 earthquake. In the months from January to June 2011, there was a +27.24% increase in the number of newborns (+ 91) delivered in the Obstetrics and Gynecology Unit of the San Salvatore Hospital of L'Aquila compared to the same six-month period in 2010. METHODS: Between January 2010 and December 2010, 874 women gave birth in L'Aquila. The women living outside of L'Aquila were excluded from the study. The remaining women, namely a sample of 451 individuals, were administered a questionnaire that focused on the level of stress experienced during the earthquake, and subsequently the Brief Cope. RESULTS: After the earthquake there was a +22.64% increase in the number of women who desired a pregnancy. The results of the Brief Cope show that the coping strategies used by the women in L'Aquila were active coping, planning, acceptance and positive reframing. CONCLUSIONS: The desire for motherhood was the main reason accounting for the increase in births that occurred after the earthquake. The decision to have a child was the tangible sign of adaptation to the post-traumatic stress.

49, XXXXY syndrome: an Italian child.

The 49, XXXXY syndrome is a rare sex chromosome polysomy, first described by Fraccaro and colleagues in 1960. The approximate incidence of this disorder is 1 in 85,000 male births. To date, >100 cases had been published in the literature. Patients with 49, XXXXY syndrome show some peculiar clinical features, such as mental retardation, facial dysmorphism, ambiguous genitalia, and multiple skeletal and cardiac defects. We report a new case of 49, XXXXY syndrome; the first Italian case to our knowledge.