Human papillomavirus genotyping in high-grade vaginal intraepithelial neoplasia: A multicentric Italian study.

This study aimed to analyze the human papillomavirus (HPV) genotype distribution in a large cohort of high-grade vaginal intraepithelial neoplasia (VaIN) (vaginal HSIL, VaIN2/3) patients from two Italian referral centers. We included all patients with histologically confirmed VaIN2/3 from the Department of Surgical Sciences, Sant'Anna Hospital, University of Torino, Torino, Italy, and Ospedale Maggiore della Carità, Novara, Italy, between 2003 and 2022. After the histological evaluation of formalin-fixed paraffin-embedded samples, we performed HPV genotyping with VisionArray HPV Chip 1.0. We detected HPV DNA in 94.4% of VaIN2/3 (168/178), with HPV 16 as the most prevalent genotype, accounting for 51.8% of all infections, 41.2% of VaIN2 and 77.6% of VaIN3 cases. Other frequent genotypes were HPV 58 (8.3%, 10.9% of VaIN2 and 2.0% of VaIN3), HPV 73 (5.4%, 5.0% of VaIN2 and 6.1% of VaIN3), and HPV 31 (5.4%, 6.7% of VaIN2 and 2.0% of VaIN3). 73.2% of VaIN2/3 had a single HPV genotype infection and 26.8% a multiple infection (20.8% a double infection, 4.8% a triple infection, and 1.2% a quadruple infection). Single infection was more frequently present in VaIN3 than VaIN2 (81.6% vs. 69.8%). 69.1% of single infections and 73.3% of multiple infections had one or more genotypes covered by nine-valent HPV vaccine. HPV vaccination is expected to have a large impact on reducing the incidence of vaginal intraepithelial neoplasia.

Is Assisted Reproductive Technology Linked to Fetal Asphyxia? A Retrospective Italian Case-Control Study.

Several risk factors are associated with fetal asphyxia. The main aim of this retrospective, analytical, case-control study was to determine whether assisted reproductive technologies (ART) could be considered one of these factors. In total, 162 cases of fetal asphyxia were compared to 361 controls where this event did not occur. We included 32 ART pregnancies, of which 12 were obtained through egg donations. Overall, 75% (24) of ART pregnancies experienced fetal asphyxia, suggesting ART increases the risk of fetal asphyxia by about 7 times. This finding is consistent with the literature. The pathogenesis of fetal asphyxia in ART pregnancies is currently unknown. Accordingly, this topic should be further investigated.

Pregnancy and neonatal outcomes of SARS-CoV-2 infection discovered at the time of delivery: a tertiary center experience in North Italy.

OBJECTIVES: Although the knowledge on SARS-CoV-2 infection in pregnancy has greatly improved, there is still a lack of information on its role in the later stages of gestation. The aim of this study is to investigate whether SARS-CoV-2 discovered at delivery is associated with any obstetric or neonatal complications. METHODS: A retrospective case-control study was conducted at Department of Obstetrics, University Hospital Maggiore della Carità, Novara, Italy, from March 2020 to March 2023. Pregnant women admitted were tested for SARS-CoV-2. 168 women resulted positive at the time of delivery; the women were asymptomatic or paucisymptomatic. 170 negative women were selected as controls, selecting, for each SARS-CoV-2 positive patient, the patient who gave birth right before, if negative. Demographic and anamnestic characteristics, pregnancy, labor, and neonatal outcomes were evaluated. RESULTS: SARS-CoV-2 positive patients were more likely to have gestational diabetes (13.7 vs. 5.3 %) and required less frequently intrapartum analgesia (11.3 vs. 27 %) and labor augmentation (7.3 vs. 16.5 %). Post-partum hemorrhage rate was lower (13.7 vs. 22.9 %) and a shorter length of first and second stage of labor occurred. There were no statistically significant differences between the two groups regarding the mode of delivery and neonatal outcomes. CONCLUSIONS: SARS-CoV-2 positive patients have shorter labor length and a lower incidence of postpartum hemorrhage. Fewer obstetric interventions, as well as less use of intrapartum analgesia and oxytocin, could explain these findings. Moreover, gestational diabetes could increase susceptibility to infection. SARS-CoV-2 infection discovered at the time of delivery in asymptomatic or paucisymptomatic patients does not appear to increase the rate of cesarean delivery or other obstetric complications, and neonatal outcomes have not worsened.

Plasma Redox Balance in Advanced-Maternal-Age Pregnant Women and Effects of Plasma on Umbilical Cord Mesenchymal Stem Cells.

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal-fetal complications with possible repercussions even in the long term. Here, we analyzed the changes in plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timings of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that, throughout pregnancy until after delivery in patients, the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients. They could have clinical relevance for the prevention of complications related to AMA pregnancy.

Menopausal Hormone Therapy, an Ever-Present Topic: A Pilot Survey about Women's Experience and Medical Doctors' Approach.

Background and Objective: Menopause can be associated with many clinical manifestations: vasomotor symptoms, urogenital problems, and additional psychological disturbances, such as anxiety, mood changes, and sleep alterations. The prolonged lack of hormones also increases the risk of long-term consequences. Hormone Replacement Treatment (HRT) in menopause consists of the administration of estrogen, alone or associated to progesterone, to relieve these uncomfortable disturbances and to prevent the onset of other pathologic conditions. The aim of this study is to examine the prevalence of HRT use in a sample of menopausal women and their experience with menopause and HRT. This study also investigates the knowledge of general practitioners (GPs) and gynecologists about HRT and its prescription. Materials and Methods: We conducted a cross-sectional population survey on 126 women of 50-59 years in an industrial city in the North of Italy, Vercelli (Novara), in Eastern Piedmont. We also presented a questionnaire on the topic to 54 medical doctors (GPs and gynecologists) of the same area. Results: The prevalence of HRT use in our sample was 11.9%. In total, a good percentage of the users affirmed to be satisfied with HRT. Additionally, a minority of women reported being ideally against the use of replacement hormones, were advised against using HRT by doctors, and did not use it because of the fear of side effects. We found a positive association between patient education, health care attitude, and HRT usage. A significant number of women knew about HRT from the media, and most of them were not informed by a health professional. Despite this, the interviewed doctors considered their knowledge about HRT as 'good' and would recommend HRT: only 5.6% would not prescribe it. Conclusions: Our results highlight the need for information about HRT among patients and health professionals, along with the need for more effective communication, evaluation, and suggestion of treatment.

How to Manage Endometriosis in Adolescence: The Endometriosis Treatment Italian Club Approach.

The evaluation of endometriosis in an adolescent girl is a challenging topic. The initial stage of the disease and the limited diagnostic instrument appropriate for the youth age and for its typical features can reduce the ability of the gynecologist. At the same time, missing a prompt diagnosis can delay the beginning of specific and punctual management of endometriosis, which could avoid a postponed diagnosis from 6 to 12 years, typical of adolescent girls complaining of dysmenorrhea. This article aimed to answer all the potential questions around the diagnosis and management of endometriosis in adolescents starting from a clinical case looking at the possible solution that is easily reproducible in the clinical practice.

Female genital mutilation/cutting: going beyond urogynecologic complications and obstetric outcomes.

PURPOSE OF REVIEW: Female genital mutilation/cutting (FGM/C or FGM) are procedures that involve partial or total removal of external female genitalia and other injuries to the female genital organs for non-medical reasons. Over 4 million girls are at risk of FGM annually. Since urogynecologic and obstetric complications of FGM have been extensively described and characterized, the aim of this review is to shift the focus on other aspects like perception of women, awareness of community, and knowledge of health workers. Our purpose is to highlight those aspects and understand how their grasp might help to eradicate this practice. RECENT FINDINGS: Self-perception of women with FGM changes when they emigrate to western countries; awareness of complications and awareness of their rights are factors that make women reject the practice. Women from rural areas, already circumcised, or without a secondary level education are more likely to have a circumcised daughter. Women with at least a secondary education are more likely to agree with the eradication of the practice. Lack of education and poor wealth index are factors associated with men's support of FGM. Although aware of FGM, healthcare professionals need to be trained on this topic. General practitioners play a central role in addressing patients with FGM to the right path of diagnosis and treatment and psychologists in helping them with psychological sequelae. CONCLUSION: These findings point out the future area of intervention, stressing the need of higher standard of care and global effort to eradicate this practice.

Hysteroscopy in the new media: quality and reliability analysis of hysteroscopy procedures on YouTube™.

BACKGROUND: Hysteroscopy plays a crucial role in diagnosing and managing various intrauterine pathologies. However, its execution can be influenced by patients' perception and understanding, which are often shaped by digital resources such as YouTubeTM. Given its popularity and accessibility, YouTubeTM has the potential to greatly influence patients' knowledge and expectations about this procedure, highlighting the need for accurate and reliable information. PURPOSE: This study aims to assess the reliability and quality of hysteroscopy information available to patients on YouTubeTM. Understanding the nature of information patients' access can help address their fears and potential misunderstandings about the procedure, consequently reducing the likelihood of suspension or postponement due to anxiety. METHODS: A comprehensive analysis of YouTubeTM was conducted, simulating the search process of a patient seeking information about hysteroscopy. The study evaluated the reliability and quality of 90 out of the first 100 hysteroscopy-related videos on YouTubeTM, scored by four gynecologists-two experienced hysteroscopists and two trainees. The videos were assessed for reliability and quality using the mDISCERN and Global Quality Scale (GQS) scores. RESULTS: The average mDISCERN and GQS scores for the evaluated videos were below the optimal three points, highlighting the lack of fluency, comprehensiveness, and reliability of the available information. Notably, while videos produced by experts, including doctors and professional channels, had higher scores, they still fell short of the minimum score of 3. These videos also were not considered more suitable for either patients or trainees. Videos that were assessed as reliable (mDISCERN ≥ 3) were observed to be longer and were more frequently produced by doctors. These videos were suggested more to trainees rather than patients. Similarly, videos deemed as fluent and comprehensive (GQS ≥ 3) were longer and were more often recommended to patients. CONCLUSIONS: While YouTubeTM is a widely used source of medical information, the quality and reliability of hysteroscopy videos on the platform are poor. The strategic use of selected, high-quality hysteroscopy videos can enhance procedure success and alleviate patient fears. However, the unsupervised discovery of information by patients could potentially lead to procedure failure or an elevated level of stress due to misleading or incorrect information.

"Better late than never but never late is better", especially in young women. A multicenter Italian study on diagnostic delay for symptomatic endometriosis.

PURPOSE: The aim of the study was to assess the length of diagnostic delay of symptomatic endometriosis in Italy and analyse the presence of correlations between the socio-demographic status of patients and the clinical characteristics/type of diagnosis. MATERIALS AND METHODS: This multicenter cross-sectional questionnaire-based study was conducted in 10 tertiary Italian referral centres for diagnosis and treatment endometriosis. A total of 689 respondents with histologically proven endometriosis and onset of the disease with pain symptoms completed an on-line self-reported questionnaire written in their own language (World Endometriosis Research Foundation-Endometriosis Phenome and Biobanking Harmonisation Project-Endometriosis Patient Questionnaire-Minimum) evaluating endometriosis related symptoms, family history of endometriosis and chronic pelvic pain, demographic data, as well as medical, reproductive, and obstetric history. RESULTS: The mean diagnostic delay found was of 11.4 years. The mean time (14.8 years) from symptoms onset to diagnosis was significantly longer among patients aged 9-19 vs patients aged 20-30 (mean 6.9 years, p < 0.001) and patients aged 31-45 (mean 2.9, p < 0.001). No significant association were found between a delayed diagnosis and any of the clinically relevant factors such as the number or severity of the reported symptoms, familiarity, hormonal therapy intake or methodology of diagnosis. CONCLUSIONS: The mean diagnostic delay of endometriosis in Italy is about 11 years. The delay can be up to 4 years longer in patients with pain symptoms onset under 20 years. Educating clinicians and patients on pathologic nature of endometriosis related pelvic pain is advisable to reduce waiting time to diagnosis, especially for young women.

Aggressive Pelvic Angiomyxoma in a Patient with Twin Pregnancy: Diagnosis, Treatment, and Clinical Complications in Light of the Literature.

(1) Background: Aggressive angiomyxoma is a mesenchymal cancer that is rare during pregnancy. It is a neoplasm that relapses and infiltrates the nearest structures. Our aim is to evaluate the management and outcomes of an observed case, in light of the current literature. (2) Methods: We observed this condition at the "Maggiore della Carità" Hospital in Novara (Italy) in a patient with an initial twin pregnancy and a suspected pelvic mass. The words "angiomyxoma" and "pregnancy" were searched on the main online scientific search sources (PubMed, Google Scholar, Scopus, WES, and Embase, etc.). (3) Results: The patient underwent surgery with a complicated follow-up, but recent negative controls. We analyzed the literature about the topic and found only 24 similar clinical cases. (4) Conclusions: Considering the current literature, it is useful to assess an aggressive angiomyxoma in the differential diagnosis of soft masses in pregnant women. The treatment of choice is surgical excision, and vaginal delivery is feasible. The therapeutic decision depends on each case.

Intrapartum cardiotocography: an exploratory analysis of interpretational variation.

Our aim was to evaluate the intra- and inter-operator agreement in cardiotocography (CTG) traces analysis using the 2015 FIGO classification guidelines, and whether the educational background and the knowledge of anamnestic data can influence the interpretation of CTG traces. A retrospective interpretation of 73 intrapartum CTGs at time 0 (T0) for a first blind interpretation and at time 1 (T1) two months later with additional anamnestic pregnancy information was made by eight different operators (four obstetricians and four midwives with different years of work experience). The intra-observer agreement demonstrates that midwifes are more concordant than obstetricians with a mean of 77.05% versus a mean of 65.75%. There is moderate inter-observer agreement in classifying a CTG trace as 'normal'; on the contrary, there is no consensus on the 'suspect' and 'pathological' classification category.IMPACT STATEMENTWhat is already known on this subject? Interpretation of intrapartum CTG is affected by significant subjective variables with relevant intra- and inter-observer lack of optimal agreement, especially in case of abnormal o pathologic findings.What do the results of this study add? Clinical data seem to play a role in interpretation of suspicious and pathological traces while they do not affect the rate of agreement for normal traces. Midwives tend to be less influenced by anamnestic data in visual CTG interpretation. Instead, obstetricians tend to be more focussed on clinical data and clinical setting that, as a consequence, tend to have great impact on CTG trace interpretation.What are the implications of these findings for clinical practice and/or further research? Cooperation among obstetricians and between obstetricians and midwives should be encouraged in order to optimise CTG reading and improve maternal and neonatal outcomes. Regarding the influence of clinical parameters in classification of intrapartum CTG traces, especially in case of abnormal CTG traces, it should be conceivable to improve medical skills in CTG blind interpretation and further investigate which clinical parameters are mainly related with an augmented risk of foetal asphyxia and adverse neonatal outcomes.

Occurrence of smooth endoplasmic reticulum aggregates in metaphase II oocytes: relationship with stimulation protocols and outcome of ICSI and IVF cycles.

STUDY QUESTION: Is there any association between the appearance of smooth endoplasmic reticulum aggregates (SERa) in oocytes and ovarian stimulation, embryological, clinical and neonatal outcomes of ICSI and IVF cycles? SUMMARY ANSWER: A suboptimal prolonged ovarian stimulation is detrimental to oocytes by inducing the occurrence of SERa, which reduces the reproductive potential of oocytes. WHAT IS KNOWN ALREADY: Controlled ovarian stimulation recruits oocytes of different qualities. Based on current evidence, it was agreed that non-homogeneous cytoplasm may represent the normal variability among oocytes rather than a dysmorphism with developmental significance. The only exception is the appearance of SERa within the ooplasm. Owing to the lack of univocal evidence in this literature about the safety of injecting oocytes with SERa and the mechanism responsible for the occurrence of SERa, this topic is still a matter of debate. STUDY DESIGN, SIZE, DURATION: A retrospective, longitudinal cohort study performed at a tertiary level public infertility center. We included 1662 cycles (180 SERa+ and 1482 SERa-) from 1129 women (age: 20-44 years) who underwent IVF/ICSI treatments in 2012-2019. The SERa+ cycles had at least one SERa+ oocyte in the oocyte cohort. The SERa- cycles had morphologically unaffected oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected stimulation data and embryological, clinical, neonatal outcomes of SERa- and SERa+ cycles and oocytes. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 347 out of 12 436 metaphase II oocytes (2.8%) were affected by SER. We performed only 12 transfers involving at least one SERa+ embryo. Stimulation length (P = 0.002), serum progesterone (P = 0.004) and follicle size (P = 0.046) at trigger, number of retrieved (P = 0.004) and metaphase II (P = 0.0001) oocytes were significantly higher in SERa+ than SERa- cycles. Fertilization rate was significantly (P < 0.0001) reduced in SERa+ cycles and oocytes compared to SERa- counterparts. Embryos of SERa+ cycles had a lower blastocyst formation rate compared to embryos of SERa- cycles (P = 0.059). Statistical analysis according to a generalized estimating equation model performed at patient level demonstrated that the duration of ovarian stimulation was predictive of SERa+ oocytes appearance. The clinical success of SERa+ cycles was lower than SERa- cycles, although no differences in neonatal birthweights or malformations were recorded in sibling unaffected oocytes of SERa+ cycles. LIMITATIONS, REASONS FOR CAUTION: Given that SERa+ oocytes were discarded in our center for years and transfers of embryos originating from affected oocytes were generally avoided, clinical outcomes of SERa+ cycles are largely attributable to the transfer of embryos derived from unaffected oocytes of SERa+ cycles and we did not have data about newborns from affected oocytes, since none of the transfers involving SERa+ embryos resulted in a progressive clinical pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: For the first time, we speculate that the late-follicular phase elevated serum progesterone caused by a suboptimal prolonged ovarian stimulation may be detrimental to the oocytes by inducing the occurrence of SERa, resulting in negative effects on their reproductive potential. This raises the question of whether some stimulation regimens could be worse than others and a change in stimulation protocol would reduce the possibility of producing oocytes with suboptimal maturation. In particular, our data highlight the importance of correct timing of the trigger in order to maximize oocyte collection, not only in terms of numerosity but also their reproductive potential. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Pronuclear score improves prediction of embryo implantation success in ICSI cycles.

BACKGROUND: In assisted reproduction technology embryo competence is routinely evaluated on morphological criteria but efficacy remains relatively low. Additional information could be obtained by evaluating pronuclear (PN) morphology. Up to now controversial results have been reported about the prognostic value of PN score. One of the main limitations of literature data is the use of different PN classification methods. In this regard, in 2011 the ESHRE and Alpha Scientists in Reproductive Medicine defined three PN categories to standardize zygote assessment. In this study we evaluated whether the consensus ESHRE-Alpha system for the pronuclear scoring could be an useful additional criterion to improve prediction of embryo implantation potential. METHODS: This is a retrospective, longitudinal, observational, cohort study. We included 3004 zygotes from 555 women who underwent ICSI treatment at our Center between January 2014 and June 2019. The PN were categorized as score 1: symmetrical, 2: non-symmetrical, 3: abnormal. A subset of 110 zygotes did not cleaved. On day 2-3 1163 embryos were transferred, 232 arrested, and 9 were cryopreserved. Among the 1490 embryos cultured up to day 5-7, 516 became blastocysts: 123 were transferred on day 5 and 393 were cryopreserved. Comparisons of age, cleavage and blastocyst rate, quality of embryos, implantation success among PN score groups were evaluated by chi-square test or Kruskal-Wallis test as appropriate. Potential predictors of embryo implantation were first tested in univariable analysis using generalized estimating equations taking into account correlation between embryos originated from the same patient. Then, variables potentially associated with implantation success (P<0.05) were included in a multivariable analysis for calculating the adjusted odds ratio (OR) and 95% confidence interval (CI). RESULTS: There was no significant difference in patients'age, cleavage and blastulation rates, and embryo morphology among the three PNscore groups. The PN score 1-embryos had a greater implantation success respect to score 2-3-ones (OR 1.83; 95% CI 1.34-2.50, P=0.0001). Consistently, the pronuclear score remained predictive of implantation in top quality embryos (OR 1.68; 95%CI 1.17-2.42, P= 0.005). CONCLUSIONS: The consensus pronuclear score may be routinely included among criteria for embryo evaluation to increase patients' chance of becoming pregnant.

Contraception in cancer survivors: insights from oncofertility follow-up visits.

OBJECTIVE: Current literature suggests that cancer survivors are less likely to receive adequate contraception counseling. However, limited data existed on barriers to contraception usage in this population and on the efficacy of dedicated consultations. This study aims to describe how contraception is perceived by cancer survivors after counseling and acceptance rates of highly effective contraceptives. METHODS: We retrospectively analyzed clinical records from 313 consecutive cancer survivors at their first follow-up visit at the Oncofertility Unit of a tertiary hospital, from 2014 to 2019. Contraception acceptance and choice were examined stratified for the type of malignancy (hormone-sensible or not). A multivariate logistic regression model was used to evaluate possible predictors of acceptance. RESULTS: Thity-three women were excluded from the analysis because trying to conceive or already pregnant. Out of the remaining 280, only 9 (3.2%) asked spontaneously for contraception, in all the other visits the issue was brought up by the physician. After counseling 44.3% of the women without contraindications still opted out effective methods for fear of hormones or refusal of more medications. Age < 33 years and being in a relationship were correlated with acceptance. CONCLUSIONS: Even after a complete counseling in a dedicated service, fears of hormones and refusal of more medications remain strong issues for these patients. Family planning needs to be discussed with cancer survivors, preferably in the context of a long-term healthcare relationship. The Oncofertility Unit should become a privileged place for this type of counseling.

Vulvovaginal atrophy of menopause and its impact on sexual function in an Italian clinical cohort of post-menopausal women.

The aim of current study was to estimate the impact of vulvovaginal atrophy (VVA) on sexual function in a clinical population of Italian postmenopausal women. Women aged 45-75 years with at least one VVA symptom completed three questionnaires: Day-to-Day Impact of Vaginal Aging (DIVA), Female Sexual Function Index (FSFI) and Female Sexual Distress Scale revised (FSDS-R). A gynaecological examination was performed for VVA confirmation. Among the 1,066 evaluable patients, VVA was confirmed in around 90% of the sample. Sexual function impairment was significantly higher in patients with confirmed VVA as observed by significant differences in the sexual function component of the DIVA questionnaire (p = .014), the FSDS-R (p < .0005), and the FSFI (p < .0005), as well as for all the FSFI subdomains: desire (p < .0005), arousal (p < .0005), lubrication (p < .0005), orgasm (p < .0005), satisfaction (p < .0005) and pain (p < .0005). Significant impairment of sexual function was demonstrated in Italian postmenopausal women who were clinically confirmed with signs of VVA through gynaecological examination.IMPACT STATEMENTWhat is already known on this subject: At least half of postmenopausal women report VVA associated symptoms with significant impact on sexual function and ultimately on sexual activity.What the results of this study add: As compared with patients without confirmed VVA, the negative impact on sexual function was significantly higher in patients with confirmed VVA. This difference was observed for the sexual function component (DIVA-C) of the DIVA questionnaire, for the overall FSDS-R result, and for the overall FSFI score, as well as for all the FSFI subdomains (desire, arousal, lubrication, orgasm, satisfaction and pain).What the implications are of these findings for clinical practice and/or further research: An impairment of sexual function is significantly associated with VVA diagnosis in Italian post-menopausal women, especially when diagnosis was objectively confirmed by clinical signs of VVA visible in the gynaecological examination. In addition, this study demonstrates that inquiring about VVA using a structured questionnaire may increase the diagnosis of VVA related changes in sexual function.

Acute abdominal pain in non-pregnant endometriotic patients: not just dysmenorrhoea. A systematic review.

Endometriosis, defined as the presence of functional endometrial tissue outside the uterine cavity, presents mainly with pelvic pain and infertility. Acute abdominal pain in non-pregnant patients with endometriosis might be minimised as a typical feature of the disease, while endometriosis is rarely considered in the differential diagnosis of acute abdominal pain. Our objective was to conduct a systematic review of the current literature of cases of acute abdomen/acute abdominal pain in non-pregnant endometriotic patients. We performed a PubMed/MEDLINE search of studies published from January 1990 to December 2018, selecting English language reports and series of non-pregnant patients with acute abdomen and histological confirmation of endometriosis. The studies were revised by two independent authors. Data were abstracted and compiled for analysis. Fifty articles reporting 62 patients were identified. The complications were classified according to anatomical sites in bowel, urinary tract, and genital organs emergencies. Rarely was the first diagnostic hypothesis endometriosis, misdiagnosis was frequent. The time frame from symptoms onset to management was often long. This is the first systematic review evaluating acute abdomen/acute abdominal pain in non-pregnant endometriotic patients. These conditions are rare but possibly life-threating and require prompt diagnosis and emergent medical or surgical treatment.

Influence of age on response to controlled ovarian stimulation in women with low levels of serum anti-Müllerian hormone.

This study aims at detecting and evaluating differences in quantitative response to controlled ovarian stimulation (COS) with high doses of gonadotropins in women with low serum anti-Müllerian hormone (AMH). About 369 first cycles in a real-life scenario in women between 21 and 43 years old and with AMH ≤0.9 ng/ml were analyzed. Older women had a significantly worse outcome with respect to young women, not only qualitatively, but also in terms of quantitative ovarian response to COS [odd ratio (OR) to obtain at least three MII oocytes with each increasing year of female age: 0.89, 95% CI: 0.85 - 0.94; p < .001]. This study endorses that age is a significant factor when counseling patients with low AMH. AMH levels per se are not a reason to exclude patients from a COS treatment, since pregnancy and live birth can be achieved, especially in younger patients. However, with an AMH equally low, the ovarian response worsens with age, making questionable the effectiveness of a stimulation with high-dose gonadotropins in the older subgroup.

Non-invasive mitochondrial DNA quantification on Day 3 predicts blastocyst development: a prospective, blinded, multi-centric study.

In ART, embryo quality evaluation is routinely based on morphological criteria. We previously demonstrated that the mitochondrial DNA (mtDNA)/genomic DNA (gDNA) ratio in culture medium was significantly associated with embryo quality and viability potential. The purpose of this prospective, blinded, multi-centric study was to validate the use of mtDNA/gDNA ratio in Day 3 spent medium as a predictor of human embryo developmental competence. The mtDNA/gDNA ratio was assessed in Day 3 culture media (n=484) of embryos from 143 patients by quantitative PCR. A mixed effect logistic regression model was applied. We found that mtDNA/gDNA ratio in Day 3 culture medium combined with embryo morphology improves the prediction upon blastulation compared to morphology alone (P < 0.0001), independent of patient and cycle characteristics. With regard to routine use in clinics, we evaluated the ability of the novel, combined grading score to improve selection of developmentally competent embryos of a single cohort. Including embryos from 44 patients, the sensibility and specificity of the scoring system based on Day 3 morphological stage were 92% and 13%, respectively. Integration with the culture medium mtDNA/gDNA ratio increased the performance of the method (sensibility: 95%; specificity: 65%). The results of this study suggest the possibility of carrying out a non-invasive evaluation of embryonic mtDNA content through the culture medium. When combined with embryo morphology, it has the potential to help embryologists rank embryos and choose which embryo(s) has the greater development potential, and thus should be transferred on Day 3, among sibling embryos with the same morphological grade.

Beyond fertility preservation: role of the oncofertility unit in the reproductive and gynecological follow-up of young cancer patients.

STUDY QUESTION: Are there reasons that motivate young cancer survivors to ask for follow-up visits at an oncofertility unit? SUMMARY ANSWER: Cancer survivors request oncofertility follow-up visits for the management of treatment-related side effects or ovarian reserve evaluation, even if not (or not yet) wishing for a pregnancy. WHAT IS KNOWN ALREADY: Personalised oncofertility counselling before gonadotoxic therapies is considered standard of care for young women with newly diagnosed cancer. However, the long-term follow-up of these patients in an oncofertility unit is not described in the literature other than for the use of cryopreserved material. STUDY DESIGN, SIZE, DURATION: We retrospectively examined rates and reasons for the first follow-up visits of 154 consecutive young female cancer patients (age range: 18-40 years) who underwent a pre-treatment consultation between January 2012 and June 2017. Demographic and clinical data were collected, as well as information about the chosen fertility preservation method, if any. PARTICIPANTS/MATERIALS, SETTING, METHODS: Rates and reasons for follow-up visits were collected and expressed as percentages. Different reasons were examined in the whole cohort and stratified for type of malignancy. Possible predictive factors for return to the follow-up visit (age, nulliparity, presence of a partner, neoplasm, having cryopreserved material) were investigated through logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Out of 154 patients, 74 returned to the oncofertility unit (48.1%) for a follow-up visit. The first visit was requested mostly at the end of anticancer therapies (51.3% versus 40.5% during therapies and 8.1% after cancer relapse). Among these patients, only 10.8% returned for the first time because they were actively desiring a pregnancy. For the others, the most common reasons for consultations were management of gynecological adverse effects of therapies (29.7%) and evaluation of ovarian reserve not linked to an immediate desire for a pregnancy (39.2%). Other patients asked for contraception (4.1%), menopause counselling (5.4%), or new fertility preservation counselling because of cancer relapse (10.8%). None of the examined factors were significantly predictive of return to the oncofertility unit. LIMITATIONS, REASONS FOR CAUTION: These findings represent the experience of a single centre. A longer duration of follow-up would be needed to provide more precise information on this regard. WIDER IMPLICATION OF THE FINDINGS: The role of an oncofertility unit should not be limited to proposing fertility preservation procedures. In the management of young adult cancer patients, the reproductive medical specialist should be considered a key figure not only before but also during and after anticancer treatments to explore salient aspects of gynecological and reproductive health. STUDY FUNDING/COMPETING INTEREST(S): This research did not receive any specific funding. M.L. served as a consultant for Teva and received honoraria from Theramex outside the submitted work. The other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N.A.

Impact of infertility and infertility treatments on quality of life and levels of anxiety and depression in women undergoing in vitro fertilization.

This study aims to evaluate levels of anxiety and depression in women, correlated with infertility per se and with infertility treatments, highlighting predictors of higher levels of distress. Two validated standardized questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Fertility Quality of Life (FertiQoL), were administered to 89 women both before their first cycle of infertility treatment and again at the end of the ovarian stimulation for in vitro fertilization (IVF). Women's levels of anxiety were significantly higher before the treatment than during the treatment itself. Stratifying the women in three groups based on principal cause of infertility (male infertility, female infertility, or both male and female), we found significantly higher levels of anxiety and general distress in patients under treatment for female infertility. Higher anxiety levels in our sample before the treatment are probably an effect of not knowing what they are expected to do to solve their problem. Moreover, when the cause of infertility is exclusively female, women experience higher levels of anxiety and general distress both before and during the treatment, probably correlated to a sense of guilt. These data help the treating physician to better counsel patients and to provide a more focused psychological support.