Healthy preterm newborns: Altered innate immunity and impaired monocyte function.

Birth prior to 37 completed weeks of gestation is referred to as preterm (PT). Premature newborns are at increased risk of developing infections as neonatal immunity is a developing structure. Monocytes, which are key players after birth, activate inflammasomes. Investigations into the identification of innate immune profiles in premature compared to full-term infants are limited. Our research includes the investigation of monocytes and NK cells, gene expression, and plasma cytokine levels to investigate any potential differences among a cohort of 68 healthy PT and full-term infants. According to high-dimensional flow cytometry, PT infants have higher proportions of CD56+/- CD16+ NK cells and immature monocytes, and lower proportions of classical monocytes. Gene expression revealed lower proportions of inflammasome activation after in vitro monocyte stimulation and the quantification of plasma cytokine levels expressed higher concentrations of alarmin S100A8. Our findings suggest that PT newborns have altered innate immunity and monocyte functional impairment, and pro-inflammatory plasmatic profile. This may explain PT infants' increased susceptibility to infectious disease and should pave the way for novel therapeutic strategies and clinical interventions.

D-chiro-inositol in clinical practice: A perspective from The Experts Group on Inositol in Basic and Clinical Research (EGOI).

BACKGROUND: D-chiro-inositol is a natural molecule that, in association with its well-studied isomer myo-inositol, may play a role in treating various metabolic and gynecological disorders. OBJECTIVES: This perspective seeks to explore the mechanisms and functions of D-chiro-inositol, laying the foundations to discuss its use in clinical practice, across dysmetabolism, obesity, and hormonal dysregulation. METHODS: A narrative review of all the relevant papers known to the authors was conducted. OUTCOME: D-chiro-inositol acts through a variety of mechanisms, acting as an insulin sensitizer, inhibiting the transcription of aromatase, in addition to modulating white adipose tissue/brown adipose tissue trans differentiation. These different modes of action have potential applications in a variety of therapeutic fields including: PCOS, dysmetabolism, obesity, hypoestrogenic/hyperandrogenic disorders, and bone health. CONCLUSIONS: D-chiro-inositol mode of action has been studied in detail in recent years, resulting in a clear differentiation between D-chiro-inositol and its isomer myo-inositol. The insulin sensitizing activities of D-chiro-inositol are well understood; however, its potential applications in other fields, in particular obesity and hyperestrogenic/hypoandrogenic disorders in men and women, represent promising avenues of research that require further clinical study.

Phyto-progestins for the treatment of abnormal uterine bleeding without organic cause in women at high risk for breast cancer and breast cancer survivors: a prospective, pilot study.

OBJECTIVES: Some plants, such as Dioscorea Villosa (DV), Vitex Agnus Castus (VAC) and Turnera diffusa (D) have some 'progesterone-like' properties. We have investigated their simultaneous administration in breast cancer (BC) survivors or carriers of specific genetic mutations that can increase the risk of developing BC suffering from abnormal uterine bleeding without organic cause. METHODS: Women with irregular cycles in terms of length (interval between ≤ 24 or ≥ 38 days) without a uterine organic disease (polyps, adenomyosis, fibroids, hyperplasia/malignancy) were included. A daily diary of bleeding, questionnaires about health-related quality of life (Short Form 36) and menstrual psychophysical well-being (PGWB-1) and the Greene Climacteric Scale (GCS) (in women older than 40 years old) questionnaire were used. The presence of some premenstrual syndrome (PMS) symptoms was also evaluated. RESULTS: In the analyzed group of women (n = 15), all experienced a regularization of the menstrual cycles, with a mean duration in the three months of use of 27.1 ± 3.2 days, with a significant reduction of menstrual pain (p = 0.02) and flow (p = 0.02) intensity. Women with PMS (7/15) reported an impovement in depression, headache and abdominal pain scores (p < 0.05). No specific deterioration of different questionnaires evaluated during treatment were observed. General satisfaction with the treatment was 6.8 ± 0.3/10 on a 10 point. CONCLUSIONS: A combination of DV, VAC and D could be a promising candidate to treat menstrual irregularities without an organic cause, with a significant reduction of menstrual pain and flow intensity and possible additional benefits in PMS symptoms treatment in women at genetic risk for BC and BC survivors.

Exposure to Prolonged Rupture of Membranes at Term Increases the Risk for Ventilatory Support in Uninfected Neonates.

OBJECTIVE: The effects of prolonged rupture of membranes (ROMs) on perinatal outcomes are still unclear, and it remains controversial for the management of those labors. This study aims to evaluate how the exposure of pregnant women to a prolonged ROM (≥ 24 hours) affects maternal and neonatal outcomes. STUDY DESIGN: This retrospective cohort study included singleton pregnant women at term delivering between January 2019 and March 2020 in a tertiary hospital. All relevant sociodemographic, pregnancy, and perinatal variables (maternal age, prepregnancy body mass index, labor, and delivery outcomes) were collected anonymously. Data were compared between the "ROM < 24 hours" and "ROM ≥ 24 hours" study groups. RESULTS: A total of 2,689 dyads were included in the study and divided according to their ROM-delivery time: ROM <24 hours (2,369 women, 88.1%), and ROM ≥ 24 hours (320 women, 11.9%). Maternal baseline characteristics were comparable except for the rate of nulliparous women, which was significantly higher among patients with ROM ≥ 24 hours. No significant differences were found regarding infectious neonatal outcomes. However, mechanical ventilation and continuous positive airway pressure were more common among neonates born after ROM ≥ 24 hours. The greater likelihood of neonatal respiratory distress was also confirmed among infants born to Group-B Streptococcus-negative women with ROM ≥ 24 hours (15 out of 267 neonates, 5.6% vs. 52 out of 1,529 with ROM < 24 hours, 3.4%, p = 0.04). CONCLUSION: According to the actual expectant policy, prolonged ROM is associated with an increased risk of respiratory support in noninfected neonates. Further investigations are required to explain such an association. KEY POINTS: · The management of women with prolonged rupture of membranes is controversial.. · The exposure of pregnant women to a prolonged rupture of membranes affects neonatal outcomes.. · Prolonged rupture of membranes is associated with an increased risk of respiratory support, in group-B Streptococcus-negative neonates..

Drospirenone 4 mg in a 24 + 4 regimen in women with contraindications to oestrogen use for contraception: bleeding patterns according to previous menstrual characteristics.

PURPOSE: A new POP consisting of 4 mg drospirenone (DRSP) for 24 days with a 4-day hormone-free interval was developed to improve bleeding predictability during POP use. The aim of this study was to evaluate the effect on bleeding patterns during use of this oral contraceptive (OC) in comparison with previous menstrual cycles before the start of OC use. METHODS: This is a pilot, prospective trial. A diary was used to collect information about daily bleeding and pelvic pain before and during treatment. During OC use, women were categorised as having (1) unscheduled bleeding or spotting days (UB), (2) scheduled bleeding or spotting days (SB) and (3) absence of bleeding/spotting (AB). SF-36 and FSFI questionnaires were used to quantify health-related quality of life and the quality of sexual life in sexually active participants. RESULTS: Eighteen out of twenty-five (72%) women completed the entire follow-up. Women with UB (44.4%) were older at inclusion (p < 0.001) and had higher BMIs (p = 0.02) than those with AB (22.2%) or SB (33.4%). Women recorded a significant reduction of menstrual flow intensity during OC use (p < 0.0001). Those with UB also experienced a significant reduction of menstrual pain intensity (p = 0.006). Women with SB during OC use had a longer baseline cycle than those who reported UB during OC use (p = 0.008). Satisfaction with this OC was very high (8.4 ± 2.2 points) with no modification in SF-36 and FSFI values. CONCLUSION: A DRSP-only pill is a good OC option for women with contraindications to oestrogen use. Features of the menstrual cycle before the start of OC use may be used to predict associated changes in bleeding patterns.

Can immunohistochemistry improve the pathological diagnosis of placenta accreta spectrum (PAS) disorders?

PURPOSE: The term of placenta accreta spectrum (PAS) disorder includes all grades of abnormal placentation. It is crucial for pathologist provide standardized diagnostic assessment to evaluate the outcome of management strategies. Moreover, a correct and safe diagnosis is useful in the medico-legal field when it becomes difficult for the gynecologist to demonstrate the suitability and legitimacy of demolitive treatment. The purposes of our study were: (1) to assess histopathologic features according to the recent guidelines; (2) to determine if immunohistochemistry can be useful to identify extravillous trophoblast (EVT) and to measure the depth of infiltration into the myometrium to improve the diagnosis of PAS. METHODS: The retrospective study was conducted on 30 cases of gravid hysterectomy with histopathologic diagnosis of PAS. To identify the depth of EVT, immunohistochemical stainings were performed using anti MNF116 (cytokeratins 5, 6, 8, 17, 19), actin-SM, HPL (Human Placental Lactogen), vimentin and GATA3 antibodies. RESULTS: Our cases were graded based on the degree of invasion of the myometrium. Ten were grade 1 (33.3%), 12 grade 2 (40%) and 8 grade 3A (26.7%). EVT invasion was best seen and evident by double immunostainings with actin-SM and cytokeratins, actin-SM and HPL, actin-SM and GATA3. CONCLUSION: The role of pathologist is decisive to determine the different grades of PAS. A better understanding of the depth of myometrial invasion can be achieved by the use of immunohistochemistry affording an important tool to obtain reproducible grading of PAS. This purpose is crucial in the setting of postoperative quality reviews and particularly in the forensic medicine field.

The role of combined oral contraceptives containing norgestimate for acne vulgaris treatment: a review.

INTRODUCTION: Both Food and Drugs Administration and European Medicine Agency (EMA) approve the use of a triphasic combined oral contraceptive (COC) containing ethinyl-oestradiol (EE) and norgestimate (NGM) for acne vulgaris treatment in women requiring an effective contraception. COCs can target sebum production and may also play a role in decreasing follicular hyperkeratinisation. RESULTS: Specific advantages of the use of an anti-androgenic progestin such as NGM in this condition are presented in this review, including the lowest venous thrombosis risk in the COCs scenario, as established by the EMA, associated with a very satisfactory cycle control. The results of aggregate analysis of published data (n = 163 vs. n = 161 treated subjects) demonstrate a significant effect in comparison with the placebo of a greater than 50% reduction, in terms of inflammatory lesions (from 19.0 to 8.2), comedones (from 35.2 to 17.7) and total lesions (from 54.3 to 25.9) count. CONCLUSIONS: The choice of a triphasic combination of EE/NGM seems a referenced, highly effective, easy-to-use and safe therapeutic approach for acne vulgaris, alone or in combination with different targeted drugs.

Triphasic ethinyl-oestradiol and norgestimate is on label for mild to moderate acne vulgaris treatment worldwide, in women requiring an effective contraception. This combination demonstrated a significant effect in comparison with the placebo of a greater than 50% reduction, in terms of inflammatory lesions, comedones and total lesions count.

A new progestin-only pill (POP): the impact of drospirenone-only pill 4 mg 24 + 4 on coagulation markers and bleeding patterns.

PURPOSE: Progestin-only pills (POPs), compared to combined, are not associated with an increased risk of venous thromboembolism, but are associated with a poor cycle control. The aim of this study was to evaluate the impact of a new POP [4 mg drospirenone (DRSP) for 24 days with a 4-day hormone-free interval] on some coagulation markers (both procoagulant and fibrinolytic) and to describe its impact on bleeding patterns. MATERIALS AND METHODS: This is a prospective trial, based on serum evaluation of following coagulation markers and tests: Factor (F) X, F VIII, F V, INR, aPTT, Protein S and antithrombin III. A 'bleeding diary' was used to categorise women as having (1) unscheduled bleeding, (2) scheduled bleeding and (3) amenorrhoea. Thirty patients were followed for six 28-day intake cycles, with a follow-up at the end of the 3rd and 6th cycles. RESULTS: There was a significant decrease of F X (p = 0.03) (-5.7% at cycle 6). No significant changes have been observed for F VII, F V and INR. A significant increase in aPTT (p = 0.01 at 3 cycles), Protein S (p = 0.0006 at 3 cycles) and antithrombin III (p < 0.0001 at 3 cycles) was recorded. This non-deteriorating coagulation impact was associated with a significant and progressive reduction of days of scheduled and unscheduled bleeding in users between cycles 4 and 6 (from 1.3 ± 0.2 days at cycle 4 to 0.8 ± 0.1 days at cycle 6 and from 2.6 ± 0.4 days at cycle 4 to 0.6 ± 0.2 days at cycle 6, respectively, p < 0.0001). CONCLUSIONS: DRSP 24 + 4 use was associated with a non-deteriorating effect on coagulation markers and a significant progressive reduction of days of scheduled and unscheduled bleeding.

Contraception with DRSP 24 + 4 was associated with a non-deteriorating effect on coagulation markers and a significant progressive reduction of days of scheduled and unscheduled bleeding.

Vitamin D and green tea extracts for the treatment of uterine fibroids in late reproductive life: a pilot, prospective, daily-diary based study.

OBJECTIVE: The beneficial effects of Vitamin D (VD) and Epigallocatechin gallate (EGCG), a polyphenol of green tea, on the growth of uterine fibroids (UF) were previously described in vitro and in vivo. We have decided to investigate their simultaneous administration in women with UFs in late reproductive life. METHODS: >40 years old n = 16 premenopausal women with intramural (IM) or subserosal (SS) UF of ≥3 cm or several UFs of different sizes, even smaller but with a total diameter ≥3 cm but <10 cm, without further concomitant organic causes of abnormal uterine bleeding, treated with EGCG 300 mg, Vitamin B6 10 mg and VD 50 µg/day for 90 days. Women completed a diary on a daily basis to obtain information about bleeding and pelvic pain. RESULTS: We have observed a significant reduction in UF's mean size both at patient's (-17.8%, p = .03) and at single UF's level (-37.3%, p = .015). The effect was more evident in women with predominant IM (p = .016) in comparison to SS UFs. No significant changes were observed for uterine and ovarian volume and endometrial thickness during treatment. We reported a significant decrease in menstrual flow length of 0.9 day (p = .04) with no modification in cycle length, menstrual flow intensity and menstrual pain intensity. The satisfaction with treatment was in general very high, with no adverse effects reported. CONCLUSION: The concomitant administration of VD and EGCG represents a promising treatment of UF in women of late reproductive life for which hormonal manipulation is not foreseen.

Impact of endocrine disorders on stillbirth: a prospective cohort study.

OBJECTIVE: Among risk factors for SB, maternal endocrine diseases (ED), such as thyroids dysfunction and gestational diabetes mellitus (GDM), are the most frequent. This study aimed to investigate the rate of ED in a population of SB cases collected prospectively, and the relationship between these and causes of death. METHODS: This is an area-based, prospective cohort study conducted in Emilia-Romagna, Italy between January 2014 and December 2020. Data included all cases of SB (>22 weeks). RESULTS: From 2014 to 2020, 766 SB occurred out of a total of 232.506 births (SB rate:0.3/1000). The ED were present in 197/766 cases of SB (25.7%), respectively, 104 thyroid disease (52.8%), 74 GDM (37.5%), and 19 cases of concomitant GDM and thyroid disease (9.6%). Women who had SB associated with ED presented significantly higher mean maternal age (p < 0.001), BMI (p < 0.001), obesity (p < 0.001) and lower smoking habit (p = 0.02) respect with control group. Neonatal and placental weight of stillborn women with ED was significantly higher (p < 0.001) in respect to stillborn of the control group. Women with ED as associated condition (ReCODE classification), present significantly higher cases of SB caused by placenta pathologies (p = 0.009) namely abruptio placentae (p = 0.001) respect than control group. CONCLUSIONS: ED was more frequent in older and obese women experiencing SB. The main cause of death was abruptio placentae. This information can be helpful when counseling mothers with ED and planning antenatal management to prevent SB.

Nutraceuticals and polycystic ovary syndrome: a systematic review of the literature.

BackgroundThis study proposes a review of nutraceuticals used in the treatment of typical symptoms of Polycystic Ovary Syndrome (PCOS).The aim is to provide a classification of the most widely used nutraceutical supplements identifying the most effective nutraceuticals on glucose and insulin metabolism, the androgenic hormone profile, fertility, ovulatory capacity, inflammation, and oxidative stress.Material and MethodsWe included randomized controlled trials on PCOS patients undergoing administration of nutraceuticals, in particular vitamin D, vitamin E, probiotics, and inositols. These administrations are variable in terms of dosage, single supplementation, or combined with other compounds, dosage, and duration of the intervention.ResultsThe supplementation of inositols, at the physiologic ratio of 40: 1 of myo- and D-chiro-inositols, resulted to be the most effective in improving the glucose homeostasis and fertility, with a restoration of ovulatory capacity and menstrual regularity. Other nutraceuticals are particularly effective in reducing hyperandrogenism, with promising results demonstrated by the combinations of vitamin D and probiotics, vitamin E and coenzyme Q10, and the enrichment of inositol therapy with group B vitamins. An improvement in the inflammatory status and antioxidant capacity is obtained with the co-supplementation of probiotics and selenium or with vitamin E combined with omega 3.ConclusionsInositol supplementation is effective in the treatment of insulin resistance and fertility. Probiotics reduced hyperandrogenism, inflammatory and oxidative conditions, and resulted more effective when combined with selenium. Although these results proved to be satisfactory, further studies are needed with larger samples and a more homogeneous analysis of the outcomes.

Stillbirth occurrence during COVID-19 pandemic: a population-based prospective study.

OBJECTIVES: Data collected worldwide on stillbirth (SB) rates during the Covid-19 pandemic are contradictory. Variations may be due to methodological differences or population characteristics. The aim of the study is to assess the changes in SB rate, risk factors, causes of death and quality of antenatal care during the pandemic compared to the control periods. METHODS: This prospective study is based on the information collected by the Emilia-Romagna Surveillance system database. We conducted a descriptive analysis of SB rate, risk factors, causes of death and quality of cares, comparing data of the pandemic (March 2020-June 2021) with the 16 months before. RESULTS: During the pandemic, the SB rate was 3.45/1,000 births, a value in line with the rates of previous control periods. Neonatal weight >90th centile was the only risk factor for SB that significantly changed during the pandemic (2.2% vs. 8.0%; p-value: 0.024). No significant differences were found in the distribution of the causes of death groups. Concerning quality of antenatal cares, cases evaluated with suboptimal care (5.2%) did not change significantly compared to the control period (12.0%), as well as the cases with less than recommended obstetric (12.6% vs. 14%) and ultrasound evaluations (0% vs. 2.7%). CONCLUSIONS: During the COVID-19 pandemic, no significant differences in SB rates were found in an area that maintained an adequate level of antenatal care. Thus, eventual associations between SB rate and the COVID-19 infection are explained by an indirect impact of the virus, rather than its direct effect.

Screening for Low-Tract Genital Infections in Women with Threatened Preterm Labor: Which Role?

OBJECTIVES: The aim of this study was to evaluate the possible relationship between cultural specimens and preterm birth in women admitted for threatened preterm labor. Preterm birth is the leading cause of neonatal mortality and antenatal hospitalization; several risk factors including intrauterine infections have been identified, but its real causes remain poorly understood. DESIGN: This is a retrospective, multicenter, cohort study including 250 women admitted for threatened preterm labor. Methods, Participants/Materials, Setting: All women admitted for threatened preterm labor, i.e., presenting with cervical changes and uterine activity before 37 weeks at the obstetrics unit of the hospitals of Modena, Monza, Carate, and Vimercate were included in the study. We excluded twin pregnancies and cases with preterm premature rupture of membranes at admission. Data about maternal history, pregnancy complications, cervical length, vaginal swabs, and urine culture at admission and gestational age at delivery were collected from clinical records in order to compare the incidence of preterm birth according to some known risk factors, cervical length, and microbiological test at admission. RESULTS: 250 women were included in the study; preterm birth at less than 37 weeks occurred in 44.4% women admitted for threatened preterm labor. The incidence of preterm birth was not different between those with a positive or a negative vaginal swab (48.3 vs. 38.4%, p = 0.22) or positive versus negative urine culture (31.8 vs. 42.1%, p = 0.23) at admission. A shorter cervical length at admission was found in women with subsequent preterm birth (17 vs. 19.5 mm, p = 0.03). Cervical length <15 mm (OR 1.82, 95% CI: 1.03-3.23, p = 0.039) predicted the risk of preterm birth. Furthermore, only the history of a previous preterm birth (p = 0.02) and a previous uterine curettage (p = 0.045) was associated with preterm birth. LIMITATIONS: The observational and retrospective nature of the study and its small sample size are important limitations of the study. Moreover, women were not systematically or randomly assigned to the screening for vaginal or urinary infections. CONCLUSIONS: There is no evidence that the search for vaginal or urinary infections in women admitted for threatened preterm labor is helpful to identify those at increased risk of preterm birth. Although several studies have explored the role of screening for bacterial vaginosis in asymptomatic women and some studies evaluated vaginal or urinary infections in women with preterm birth, none of them focused on the possible role of microbiological specimens as a predictive tool in women admitted for threatened PTL. No association was found in our study, but prospective randomized controlled trials are required to confirm the results of this observation.

The role of vitamin D in metabolic and reproductive disturbances of polycystic ovary syndrome: A narrative mini-review.

Vitamin D is a secosteroid hormone that plays a pivotal role in several metabolic and reproductive pathways in humans. Increasing evidence supports the role of vitamin D deficiency in metabolic disturbances and infertility in women with polycystic ovary syndrome (PCOS). Indeed, supplementation with vitamin D seems to have a beneficial role on insulin resistance (IR) and endometrial receptivity. On the other hand, exceedingly high levels of vitamin D appear to play a detrimental role on oocytes development and embryo quality. In the current review, we summarize the available evidence about the topic, aiming to suggest the best supplementation strategy in women with PCOS or, more generally, in those with metabolic disturbances and infertility. Based on the retrieved data, vitamin D seems to have a beneficial role on IR, insulin sensitivity and endometrial receptivity, but high levels and incorrect timing of administration seem to have a detrimental role on oocytes development and embryo quality. Therefore, we encourage a low dose supplementation (400-800 IU/day) particularly in vitamin D deficient women that present metabolic disturbances like PCOS. As far as the reproductive health, we advise vitamin D supplementation in selected populations, only during specific moments of the ovarian cycle, to support the luteal phase. However, ambiguities about dosage and timing of the supplementation still emerge from the clinical studies published to date and further studies are required.

The use of different doses levonorgestrel-releasing intrauterine system (LNG-IUS): real-world data from a multicenter Italian study.

PURPOSE: Current research fails to adequately inform about the differential use of available levonorgestrel-releasing intrauterine systems (LNG-IUSs) in real life. Aim of our study was to compare the characteristics, satisfaction, continuation rates, and adverse effects between users of the high-dose LNG-IUS (52 mg) and of the low dose LNG-IUS (13.5 mg and 19.5 mg). MATERIALS AND METHODS: A prospective cohort study was performed in two Services for Family Planning in normal menstruating women with the inclusion of all new prescriptions of LNG-IUS for contraception. Women were followed for a mean of 9.1 ± 2.6 months after placement. RESULTS: 109 women (mean age of 39.8 ± 8.7 years old) were included, 69.7% using a high dose LNG-IUS and 30.3% using a low dose LNG-IUS. Women with a low dose LNG-IUS were significantly younger, thinner, more nulliparous, with fewer vaginal deliveries and C-sections, with a lower menstrual flow length and with more previous use of short-acting reversible contraceptives (p < 0.05). LNG-IUS continuation was similar and very high at the last follow-up: 100 vs. 94.7% in the low and high dose LNG-IUS groups, respectively (p = 0.18). Satisfaction with treatment at the end of the study was similar between different LNG-IUS doses (p = 0.85), with 78.9% being satisfied/very satisfied. Bleeding patterns were significantly different between the two LNG-IUS doses (p < 0.0001). Diagnosis of dysfunctional cysts was more frequent in women with high dose compared to low dose LNG-IUS (22.2 vs. 12.1%), albeit not significantly. CONCLUSIONS: We have shown a clear differential use of available LNG-IUS in clinical practice, both as baseline characteristics and as different outcomes, primarily for bleeding patterns. However, all these systems were associated with a very high rate of satisfaction and continuation.

BRCA mutation carriers' perception about benefits and risks associated with combined hormonal contraceptives use.

OBJECTIVE: To evaluate the actual perceptions about combined hormonal contraceptives (CHCs) use in BRCA mutation carriers in comparison to women from the general population. METHODS: This was a cross-sectional, observational study involving two Italian referral centres for hereditary cancers. An identical questionnaire investigating how CHC use could affect the risk of developing some types of cancer, specific diseases, and symptoms was administered to 85 BRCA mutation carriers and 85 healthy women without this genetic mutation (control group). Women's perceptions were evaluated using specific questions and Likert scales (-5 to +5). RESULTS: Perceptions about the effects of CHC use on developing specific diseases and symptoms did not differ between BRCA mutation carriers and controls. Conversely, the protective effects of CHC use on colorectal (p = .02), uterine body (p = .01) and ovarian (p = .01) cancers were unknown by BRCA mutation carriers. Moreover, BRCA mutation carriers recognised the association between CHC use and a higher risk of breast (p = .0008) and uterine cervix cancer (p = .007). CONCLUSIONS: Investing time and effort in transmitting the correct key messages about oncological risk related to CHC use could potentially increase their use in BRCA mutation carriers.

Perinatal outcomes in women affected by different types of headache disorders: A prospective cohort study.

OBJECTIVE: This study aims to investigate pregnancy and perinatal outcomes in women with tension-type headache, migraine without aura and migraine with aura by comparing them to women without any headache disorders. STUDY DESIGN: Prospective cohort study including singleton pregnancies attending the first trimester aneuploidy screening at the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. RESULTS: A total of 515 consecutive women were included and headache disorders were reported in 43.5% of them (224/515). Tension-type headache was diagnosed in 24.3% of the cases, while 14% suffered from migraine without aura and 5.2% from migraine with aura. Birthweight was significantly lower in women affected by migraine with aura respective to other groups, and a significantly higher rate of small for gestational age infants was found in tension-type headache (10.4%) and in migraine with aura (24.9%) groups respective to the others (p < 0.001). Moreover, the admission to the neonatal intensive care unit was significantly higher in all the headache groups (p = 0.012). Multivariate analysis showed that women presenting tension-type headache (OR 4.19, p = 0.004), migraine with aura (OR 5.37, p = 0.02), a uterine artery pulsatility index >90th centile (OR 3.66, p = 0.01), low multiple of the median (MoM) of Pregnancy-associated plasma protein-A (PAPP-A) (OR 0.48, p = 0.05) and high MoM of Inhibin-A (OR 3.24, p = 0.03) at first trimester, are independently associated with the delivery of small for gestational age infants when compared to women without headache disorders. CONCLUSION: Migraine with aura and tension type headache expose women to an increased risk of delivering small for gestational age infants, in association with some utero-placenta markers evaluated at first trimester. These women with headache disorders have an additional indication to undergo first trimester aneuploidy screening and would possibly benefit from specific interventions.

BRCA mutation carriers' perceptions on postmenopausal hormone therapy: An Italian study.

OBJECTIVE: To evaluate the actual perceptions of postmenopausal hormone therapy (HT) in BRCA mutation carriers (BRCAmc) in comparison with women from the general population. METHODS: Questionnaire-based study of 83 BRCAmc and a control group of 89 women without a genetic mutation. Perceptions were evaluated by specific questions and Likert scales (-5-+5). RESULTS: Present and past users of HT were more frequent in the control group (p = 0.01), with a longer time of use (p = 0.03). The preferred route of administration of HT was 'oral' (54.6%). The most frequently reported adverse effect of HT was venous thrombosis (0.8), while a protective effect on bone health was reported. No noticeable beneficial effects of HT have been recognised for hot flushes (0.2) and vaginal dryness (0.1). The most frequently perceived beneficial and adverse effects of HT were not significantly different between BRCA mutation carriers and controls. The greatest oncological fear was breast cancer (1.0). The protective role of HT on colorectal cancer was not known (0.1). These oncological impacts were mostly overestimated in BRCAmc, however this was not significant. Few BRCAmc would think of taking HT after risk-reducing surgeries. CONCLUSIONS: Knowledge of the effects of HT on BRCAmc is relatively poor and they are likely to overstate its negative effects and underestimate its health benefits; however, this is not significant in comparison to the general population. More and better information should be given to BRCAmc to allow them to make informed decisions about the use of HT, especially before undergoing risk-reducing surgeries.

A first trimester prediction model for large for gestational age infants: a preliminary study.

BACKGROUND: Large for gestational age infants (LGA) have increased risk of adverse short-term perinatal outcomes. This study aims to develop a multivariable prediction model for the risk of giving birth to a LGA baby, by using biochemical, biophysical, anamnestic, and clinical maternal characteristics available at first trimester. METHODS: Prospective study that included all singleton pregnancies attending the first trimester aneuploidy screening at the Obstetric Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. RESULTS: A total of 503 consecutive women were included in the analysis. The final prediction model for LGA, included multiparity (OR = 2.8, 95% CI: 1.6-4.9, p = 0.001), pre-pregnancy BMI (OR = 1.08, 95% CI: 1.03-1.14, p = 0.002) and PAPP-A MoM (OR = 1.43, 95% CI: 1.08-1.90, p = 0.013). The area under the ROC curve was 70.5%, indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to - 1.378, which corresponds to a 20.1% probability of having a LGA infant. By using such a cut-off, the risk of LGA can be predicted in our sample with sensitivity of 55.2% and specificity of 79.0%. CONCLUSION: At first trimester, a model including multiparity, pre-pregnancy BMI and PAPP-A satisfactorily predicted the risk of giving birth to a LGA infant. This promising tool, once applied early in pregnancy, would identify women deserving targeted interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04838431 , 09/04/2021.

Robot-Assisted Nerve-sparing Resection of Bilateral Parametrial Deep Infiltrating Endometriosis.

OBJECTIVE: To demonstrate the surgical steps used to perform a robotic radical parametrectomy in a woman with deep infiltrating endometriosis. DESIGN: Description of the procedure using video. SETTING: University hospital, referral center for endometriosis and minimally invasive surgery. INTERVENTIONS: A 47-year-old woman, with a body mass index of 31 kg/m2, who had undergone a supracervical hysterectomy for fibromatosis 5 years earlier, presented for definitive surgical management of parametrial and rectal endometriosis-associated pain. Robot-assisted nerve-sparing eradication of endometriosis, trachelectomy, and rectal shaving were planned. On the right side, the retroperitoneum was opened to widely expose the ureter, and a right adnexectomy was performed, gently separating the ureter from the diffuse periadnexal fibrosis. Right medial pararectal space was developed, and after right partial uterolysis, a nerve-sparing resection of the posterior parametrial endometriosis was performed. On the left side, endometriotic infiltration penetrated into the lateral and anterior (cranial portion) parametrium, wrapping the left uterine artery and the ureter. Left paravesical and pararectal spaces were developed. The left uterine artery was clipped at its origin, and the resection of the lateral and anterior parametrial nodules was completed following the shape of the nodule, dividing the lesion in 2 parts, and following the plane of the deep uterine vein to avoid excision of the nerve branches from the left inferior hypogastric plexus. Rectal endometriosis was removed by shaving, and the surgery ended with trachelectomy and robotic suture of the vaginal cuff. CONCLUSION: Robot-assisted laparoscopy is a safe and effective technique for nerve-sparing resection of parametrial endometriosis.