Jessica Ottolina

@hsr.it

Obst and Gyn
San Raffaele Hospital

RESEARCH INTERESTS

endometriosis, infertility, reproductive surgery

51

Scopus Publications

Scopus Publications

  • Extracellular vesicles secreted by human aneuploid embryos present a distinct transcriptomic profile and upregulate MUC1 transcription in decidualised endometrial stromal cells
    Sofia Makieva, Elisa Giacomini, Giulia Maria Scotti, Dejan Lazarevic, Valentina Pavone, Jessica Ottolina, Ludovica Bartiromo, Matteo Schimberni, Marco Morelli, Alessandra Alteri,et al.

    Oxford University Press (OUP)
    Abstract STUDY QUESTION Do extracellular vesicles (EVs) secreted by aneuploid human embryos possess a unique transcriptomic profile that elicits a relevant transcriptomic response in decidualized primary endometrial stromal cells (dESCs)? SUMMARY ANSWER Aneuploid embryo-derived EVs contain transcripts of PPM1J, LINC00561, ANKRD34C, and TMED10 with differential abundance from euploid embryo-derived EVs and induce upregulation of MUC1 transcript in dESCs. WHAT IS KNOWN ALREADY We have previously reported that IVF embryos secrete EVs that can be internalized by ESCs, conceptualizing that successful implantation to the endometrium is facilitated by EVs. Whether these EVs may additionally serve as biomarkers of ploidy status is unknown. STUDY DESIGN, SIZE, DURATION Embryos destined for biopsy for preimplantation genetic testing for aneuploidy (PGT-A) were grown under standard conditions. Spent media (30 μl) were collected from euploid (n = 175) and aneuploid (n = 140) embryos at cleavage (Days 1–3) stage and from euploid (n = 187) and aneuploid (n = 142) embryos at blastocyst (Days 3–5) stage. Media samples from n = 35 cleavage-stage embryos were pooled in order to obtain five euploid and four aneuploid pools. Similarly, media samples from blastocysts were pooled to create one euploid and one aneuploid pool. ESCs were obtained from five women undergoing diagnostic laparoscopy. PARTICIPANTS/MATERIALS, SETTING, METHODS EVs were isolated from pools of media by differential centrifugation and EV-RNA sequencing was performed following a single-cell approach that circumvents RNA extraction. ESCs were decidualized (estradiol: 10 nM, progesterone: 1 µM, cAMP: 0.5 mM twice every 48 h) and incubated for 24 h with EVs (50 ng/ml). RNA sequencing was performed on ESCs. MAIN RESULTS AND THE ROLE OF CHANCE Aneuploid cleavage stage embryos secreted EVs that were less abundant in RNA fragments originating from the genes PPM1J (log2fc = −5.13, P = 0.011), LINC00561 (log2fc = −7.87, P = 0.010), and ANKRD34C (log2fc = −7.30, P = 0.017) and more abundant in TMED10 (log2fc = 1.63, P = 0.025) compared to EVs of euploid embryos. Decidualization per se induced downregulation of MUC1 (log2fc = −0.54, P = 0.0028) in ESCs as a prerequisite for the establishment of receptive endometrium. The expression of MUC1 transcript in decidualized ESCs was significantly increased following treatment with aneuploid compared to euploid embryo-secreted EVs (log2fc = 0.85, P = 0.0201). LARGE SCALE DATA Raw data have been uploaded to GEO (accession number GSE234338). LIMITATIONS, REASONS FOR CAUTION The findings of the study will require validation utilizing a second cohort of EV samples. WIDER IMPLICATIONS OF THE FINDINGS The discovery that the transcriptomic profile of EVs secreted from aneuploid cleavage stage embryos differs from that of euploid embryos supports the possibility to develop a non-invasive methodology for PGT-A. The upregulation of MUC1 in dESCs following aneuploid embryo EV treatment proposes a new mechanism underlying implantation failure. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by a Marie Skłodowska-Curie Actions fellowship awarded to SM by the European Commission (CERVINO grant agreement ID: 79620) and by a BIRTH research grant from Theramex HQ UK Ltd. The authors have no conflicts of interest to declare.

  • How to Manage Endometriosis in Adolescence: The Endometriosis Treatment Italian Club Approach
    Lucia Lazzeri, Karin Louise Andersson, Stefano Angioni, Alessandro Arena, Saverio Arena, Ludovica Bartiromo, Nicola Berlanda, Cecilia Bonin, Massimo Candiani, Gabriele Centini,et al.

    Elsevier BV

  • CO2 fiber laser vaporization for endometrioma treatment results in preserved ovarian responsiveness and improved embryo quality in infertile women undergoing ART
    Massimo CANDIANI, Stefano M. FERRARI, Noemi SALMERI, Carolina DOLCI, Roberta VILLANACCI, Ludovica BARTIROMO, Matteo SCHIMBERNI, Iacopo TANDOI, Enrico PAPALEO, and Jessica OTTOLINA

    Edizioni Minerva Medica
    BACKGROUND Infertile women carrying ovarian endometriomas can be managed either with surgery or by in vitro fertilization (IVF). The objective of this study is to compare ovarian responsiveness to controlled ovarian stimulation (COS) in assisted reproduction techniques (ART) in infertile women carrying small intact endometriomas and those managed by endometrioma cystectomy or CO2 fiber laser ablation. METHODS Retrospective case-control study of prospectively collected data including women underwent ART for endometriosis-related infertility. The study group consisted of infertile women undergoing endometriomas CO2 fiber laser vaporization before ART ('ART after laser CO2' group). Controls were infertile women with endometrioma managed by cystectomy before ART ('ART after cystectomy' group) and infertile women with small endometriomas undergoing ART as first approach ('ART only' group). RESULTS Of the 86 included patients, 27 (31.4%) belonged to 'ART after laser CO2' group, 37 (43%) to 'ART after cystectomy' group and 22 (25.6%) to 'ART only' group. Surgical groups had larger endometriomas than patients referred to 'ART only' group. No between-groups differences were observed in terms of COS protocol, gonadotropins starting and total doses and length of COS. While women belonged to 'ART after cystectomy' group had fewer recruited follicles (p = .014), oocytes (p = .042), MII oocytes (p = .042) and formed embryos (p = .004) compared to women of 'ART only' group, no significant differences were found between patients of 'ART only' group 'ART after laser CO2' group. A greater number of good-quality embryos were observed in surgical groups. No between-groups differences were found in clinical pregnancy rates. CONCLUSIONS Our results demonstrate encouraging findings on IVF/ICSI outcomes after laser CO2 endometrioma ablation in terms of both quantity and quality of developed embryos.

  • Minimally invasive surgery for ovarian endometriosis as a mean of improving fertility: Cystectomy vs. CO2 fiber laser ablation what do we know so far?
    Massimo Candiani, Jessica Ottolina, Noemi Salmeri, Sara D’Alessandro, Iacopo Tandoi, Ludovica Bartiromo, Matteo Schimberni, Stefano Ferrari, and Roberta Villanacci

    Frontiers Media SA
    Minimally invasive surgery emerged in the 1980s as a safe and effective technique which requires smaller incisions and, usually, a shorter hospital stay compared to traditional surgery. Since then, minimally invasive surgery has expanded in many surgical specialties. One of its newest application in gynecology stands in the infertility management of young women with unexplained infertility or suspected endometriosis. In these cases, laparoscopy allows to diagnose and treat the disease aiming to increase at best the chances of spontaneous pregnancy or trough assisted reproductive technology. Nowadays, minimally invasive surgical approach of ovarian endometriosis consists of either laparoscopic cystectomy or ablative techniques such as laparoscopic CO2 fiber laser vaporization. Although cystectomy represents the gold standard according to the latest Cochrane review, some endometriosis experts are worried about its detrimental effect on healthy ovarian parenchyma and suggest preferring a less aggressive approach such as CO2 fiber laser vaporization. The aim of this review is to give an overview of the available evidences about the impact of the two surgical procedures on ovarian reserve markers and pregnancy outcome.

  • Surgery versus IVF for the treatment of infertility associated to ovarian and deep endometriosis (SVIDOE: Surgery Versus IVF for Deep and Ovarian Endometriosis). Clinical protocol for a multicenter randomized controlled trial
    Jessica Ottolina, Michele Vignali, Enrico Papaleo, Paola Viganò, Edgardo Somigliana, Stefano Ferrari, Valeria Liprandi, Gaia Belloni, Marco Reschini, Massimo Candiani,et al.

    Public Library of Science (PLoS)
    The management of endometriosis-related infertility is still a challenging issue. Women can be managed with either surgery or in vitro fertilization (IVF). The decision is tailored to the patients considering pros and cons of both approaches. Surgery might increase the chances of natural conception and relieve symptoms. IVF may be more effective, but costs are higher and unoperated women face some peculiar additional risks during the procedure and pregnancy. The unavailability of randomized trials comparing the two strategies hampers the possibility to provide precise estimates. This Randomized Controlled Trial (RCT) aims at filling this gap. This is a multicenter, non-blinded, randomized controlled trial with parallel groups and allocation 1:1. Three Italian Academic Infertility Units will be involved. Main inclusion criteria are infertility for more than one year, age less than 40 years and a sonographic diagnosis of endometriosis (ovarian endometriomas or deep peritoneal lesions). Previous IVF and previous surgery for endometriosis are exclusion criteria. Women will be randomized to either surgery and then natural pregnancy seeking or a standard program of three IVF cycles. The primary aim is the comparison of live birth rate between the two groups (IVF versus surgery) within one year of randomization. The secondary aim is the evaluation of cost-effective profile of the two interventions. The present study can influence the clinical practice of infertility treatment in women with endometriosis. From a public health perspective, information on the more cost-effective clinical management strategy would consent a wiser allocation of resources. Trial registration: NCT04743167, registered on 8 February 2021.


  • ‘Guess who’? An Italian multicentric study on pigmentation traits prevalence in endometriosis localizations
    N. Salmeri, J. Ottolina, L. Bartiromo, M. Schimberni, C. Dolci, S. Ferrari, R. Villanacci, S. Arena, N. Berlanda, L. Buggio,et al.

    Elsevier BV

  • A Systematic Review of Atypical Endometriosis-Associated Biomarkers
    L. Bartiromo, M. Schimberni, R. Villanacci, G. Mangili, Stefano Ferrari, J. Ottolina, N. Salmeri, C. Dolci, I. Tandoi and M. Candiani


    Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. We performed an advanced, systematic search of the online medical databases PubMed and Medline. The search revealed n = 40 studies eligible for inclusion in this systematic review. Of these, n = 39 were finally included. The results from included studies are characterized by high heterogeneity, but some consistency has been found for altered expression in phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, ARID1a, estrogen and progesterone receptors, transcriptional, nuclear, and growth factors in atypical endometriosis. Although many targets have been proposed as biomarkers for the presence of atypical endometriosis, none of them has such strong evidence to justify their systematic use in clinical practice, and they all need expensive molecular analyses. Further well-designed studies are needed to validate the evidence on available biomarkers and to investigate novel serum markers for atypical endometriosis.

  • Catamenial Pneumothorax as the First Expression of Thoracic Endometriosis Syndrome and Pelvic Endometriosis
    Paola Ciriaco, Piergiorgio Muriana, Angelo Carretta, Jessica Ottolina, Massimo Candiani, and Giampiero Negri

    MDPI AG
    Objective: The menstrual-related catamenial pneumothorax (CP) can be the first expression of thoracic endometriosis syndrome (TES), which is the presence of endometriotic lesions in the lungs and pleura, and pelvic endometriosis (PE). This study aims to analyze our experience with this specific correlation describing our multidisciplinary approach to CP. Methods: Hospital records of 32 women, operated for CP at our Department from January 2001 to December 2021 were reviewed. Surgical treatment consisted of videothoracoscopy and laparoscopy when indicated. Results: TES and PE were diagnosed in 13 (40.6%) and 12 (37.5%) women, respectively. The association of TES and PE was present in 11 cases (34%). Fifteen patients (46.9%) underwent laparoscopy, of which 11 concurrently with videothoracoscopy. Most of the patients affected had stage III–IV endometriosis (40.6%). All patients received hormonal therapy after surgery. Five patients with PE conceived spontaneously resulting in six live births. The mean follow-up was 117 ± 71 months (range 8–244). Pneumothorax recurrence occurred in six patients (18.8%). At present, all women are asymptomatic, with no sign of pneumothorax recurrence. Conclusions: CP might be the first expression of TES and/or PE. A multidisciplinary approach is advocated for optimal management of the disease.

  • Impact of endometriosis on obstetric outcome after natural conception: a multicenter Italian study
    N. Berlanda, W. Alio, S. Angioni, V. Bergamini, C. Bonin, P. Boracchi, M. Candiani, G. Centini, M. N. D’Alterio, S. Del Forno,et al.

    Springer Science and Business Media LLC
    Abstract Purpose To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy. Methods Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded. All women filled in a questionnaire addressing previous natural pregnancies. Marginal logistic regression models were fitted to evaluate the impact of endometriosis on obstetric outcome. A post hoc analysis was performed within the endometriosis group comparing women with severe adenomyosis versus women with absent or mild adenomyosis. Results Three hundred and fifty-five pregnancies in endometriosis group and 741 pregnancies in control group were included. Women with endometriosis had a higher risk of preterm delivery < 34 weeks (6.4% vs 2.8%, OR 2.42, 95% CI 1.22–4.82), preterm delivery < 37 weeks (17.8% vs 9.7%, OR 1.98, 95% CI 1.23–3.19), and neonatal admission to Intensive Care Unit (14.1% vs 7.0%, OR 2.04, 95% CI 1.23–3.36). At post hoc analysis, women with endometriosis and severe adenomyosis had an increased risk of placenta previa (23.1% vs 1.8%, OR 16.68, 95% CI 3.49–79.71), cesarean delivery (84.6% vs 38.9%, OR 8.03, 95% CI 1.69–38.25) and preterm delivery < 34 weeks (23.1% vs 5.7%, OR 5.52, 95% CI 1.38–22.09). Conclusion Women with endometriosis who conceive naturally have increased risk of preterm delivery and neonatal admission to intensive care unit. When severe adenomyosis is coexistent with endometriosis, women may be at increased risk of placenta previa and cesarean delivery. Trial registration Clinical trial registration number: NCT03354793.

  • Impact of COVID-19 on vascular patients worldwide: Analysis of the COVIDSurg data
    Louise HITCHMAN, Matthew MACHIN, and

    Edizioni Minerva Medica
    BACKGROUND The COVIDSurg collaborative was an international multicenter prospective analysis of perioperative data from 235 hospitals in 24 countries. It found that perioperative COVID-19 infection was associated with a mortality rate of 24%. At the same time, the COVER study demonstrated similarly high perioperative mortality rates in vascular surgical patients undergoing vascular interventions even without COVID-19, likely associated with the high burden of comorbidity associated with vascular patients. This is a vascular subgroup analysis of the COVIDSurg cohort. METHODS All patients with a suspected or confirmed diagnosis of COVID-19 in the 7 days prior to, or in the 30 days following a vascular procedure were included. The primary outcome was 30-day mortality. Secondary outcomes were pulmonary complications (adult respiratory distress syndrome, pulmonary embolism, pneumonia and respiratory failure). Logistic regression was undertaken for dichotomous outcomes. RESULTS Overall, 602 patients were included in this subgroup analysis, of which 88.4% were emergencies. The most common operations performed were for vascular-related dialysis access procedures (20.1%, N.=121). The combined 30-day mortality rate was 27.2%. Composite secondary pulmonary outcomes occurred in half of the vascular patients (N.=275, 45.7%). CONCLUSIONS Mortality following vascular surgery in COVID positive patients was significantly higher than levels reported pre-pandemic, and similar to that seen in other specialties in the COVIDSurg cohort. Initiatives and surgical pathways that ensure vascular patients are protected from exposure to COVID-19 in the peri-operative period are vital to protect against excess mortality.

  • Publisher Correction: Concomitant autoimmunity may be a predictor of more severe stages of endometriosis (Scientific Reports, (2021), 11, 1, (15372), 10.1038/s41598-021-94877-z)
    Valeria Stella Vanni, Roberta Villanacci, Noemi Salmeri, Enrico Papaleo, Diana Delprato, Jessica Ottolina, Patrizia Rovere-Querini, Stefano Ferrari, Paola Viganò, and Massimo Candiani

    Springer Science and Business Media LLC

  • Impact of Bacillus Calmette-Gue´rin (BCG) vaccination on postoperative mortality in patients with perioperative SARS-CoV-2 infection
    Covid Surg Collaborative

    Oxford University Press (OUP)
    There is little evidence around the potentially protective role of previous Bacillus Calmette-Guerin (BCG) vaccination on postoperative mortality in patients with perioperative SARS-CoV-2 vaccination. Prior BCG vaccination did not protect SARS-CoV-2 infected patients against postoperative pulmonary complications and 30-day mortality.

  • Endometriosis and phytoestrogens: Friends or foes? a systematic review
    Ludovica Bartiromo, Matteo Schimberni, Roberta Villanacci, Jessica Ottolina, Carolina Dolci, Noemi Salmeri, Paola Viganò, and Massimo Candiani

    MDPI AG
    The aim of this systematic review was to provide comprehensive and available data on the possible role of phytoestrogens (PE) for the treatment of endometriosis. We conducted an advanced, systematic search of online medical databases PubMed and Medline. Only full-length manuscripts written in English up to September 2020 were considered. A total of 60 studies were included in the systematic review. According to in vitro findings, 19 out of 22 studies reported the ability of PE in inducing anti-proliferative, anti-inflammatory and proapoptotic effects on cultured cells. Various mechanisms have been proposed to explain this in vitro action including the alteration of cell cycle proteins, the activation/inactivation of regulatory pathways, and modification of radical oxidative species levels. Thirty-eight articles on the effects of phytoestrogens on the development of endometriotic lesions in in vivo experimental animal models of endometriosis have been included. In line with in vitro findings, results also derived from animal models of endometriosis generally supported a beneficial effect of the compounds in reducing lesion growth and development. Finally, only seven studies investigated the effects of phytoestrogens intake on endometriosis in humans. The huge amount of in vitro and in vivo animal findings did not correspond to a consistent literature in the women affected. Therefore, whether the experimental findings can be translated in women is currently unknown.

  • Early outcomes and complications following cardiac surgery in patients testing positive for coronavirus disease 2019: An international cohort study
    Enoch Akowuah, Ruth A. Benson, Edward J. Caruana, Govind Chetty, John Edwards, Stefano Forlani, George Gradinariu, Gavin J. Murphy, Aung Ye Oo, Akshay J. Patel,et al.

    Elsevier BV

  • The pathogenesis of endometriosis: Clues from the immunological evidence
    Roberta VILLANACCI, Veronica BANDINI, Jessica OTTOLINA, Luca PAGLIARDINI, Massimo CANDIANI, and Paola VIGANÒ

    Edizioni Minerva Medica
    INTRODUCTION Endometriosis pathogenesis is still a matter of debate. It is now agreed that a complex cooperation of genetic, hormonal, immune and environmental factors is implicated. However, no consensus has been reached yet on what firstly is responsible for the initiation, promotion and survival of endometrial-like tissue outside the uterine cavity. Since consistent evidence have found immunological alterations in women with the disease, the impairment of immune system has been considered for decades one of the possible causes of endometriosis. The aim of this literature review is to summarize the available findings on a particular aspect of this topic represented by the inhibition of natural killer (NK) cell activity in women affected as a paradigmatic example of the complexity in studying the pathogenesis of endometriosis. EVIDENCE ACQUISITION Advanced search of PubMed for English articles published between 1990 and September 2020 using the keywords "endometriosis" or "endometrioma" or "endometriotic" or "ectopic endometrium" in combination with "natural killer cells" (NK). EVIDENCE SYNTHESIS Consistent studies have found an impairment in NK cell activity in women with endometriosis especially in advanced stages of disease (stage III/IV). Reports to explain these findings support the phenomenon as a consequence of the disease establishment. Evidence from genetic studies have questioned the role of these dysfunctions in the pathogenesis of the disease. CONCLUSIONS Immunological dysfunctions and the decreased NK cell cytotoxicity may only represent consequence of endometriosis, although the underlining mechanisms still need to be elucidated.

  • Machine learning risk prediction of mortality for patients undergoing surgery with perioperative SARS-CoV-2: The COVIDSurg mortality score
    , Laura Bravo, Dmitri Nepogodiev, James C Glasbey, Elizabeth Li, Joana FF Simoes, Sivesh K Kamarajah, Maria Picciochi, Tom EF Abbott, Adesoji O Ademuyiwa,et al.

    Oxford University Press (OUP)
    To support the global restart of elective surgery, data from an international prospective cohort study of 8492 patients (69 countries) was analysed using artificial intelligence (machine learning techniques) to develop a predictive score for mortality in surgical patients with SARS-CoV-2. We found that patient rather than operation factors were the best predictors and used these to create the COVIDsurg Mortality Score (https://covidsurgrisk.app). Our data demonstrates that it is safe to restart a wide range of surgical services for selected patients.

  • Fertility Outcome after CO<inf>2</inf> Laser Vaporization versus Cystectomy in Women with Ovarian Endometrioma: A Comparative Study
    Massimo Candiani, Stefano Ferrari, Ludovica Bartiromo, Matteo Schimberni, Iacopo Tandoi, and Jessica Ottolina

    Elsevier BV
    STUDY OBJECTIVE To assess the postoperative likelihood of conception in patients with endometriomas managed by either CO2 laser vaporization or cystectomy. DESIGN A retrospective study with prospective recording of data. SETTING University hospital. PATIENTS One hundred and forty-two patients with symptomatic endometriomas. INTERVENTIONS Patients underwent a standardized laparoscopic stripping technique (Group 1) or cyst vaporization with CO2 fiber laser (Group 2). Patients wishing to become pregnant were allowed to attempt a spontaneous conception after surgery. If spontaneous conception failed, patients were referred for in vitro fertilization (IVF). MEASUREMENTS AND MAIN RESULTS The primary objective was to compare pregnancy rates between the two groups. The secondary objective was the identification of independent predictors of pregnancy. Thirty-nine women in Group 1 (53.4%) and 39 women in Group 2 (56.5%) desired to conceive after surgery. Three patients (7.7%) in Group 1 became pregnant following donor-IVF and were excluded. Pregnancies were recorded in 72.2% of patients treated with cystectomy and in 74.3% of those managed with CO2 fiber laser (p=.83). Twenty patients (55.6%) in Group 1 and 14 patients (35.9%) in Group 2 conceived spontaneously (p=.08). Among patients who failed spontaneous conception, 21 patients (28%) achieved pregnancy through IVF (Group 1: n=6, 16.7%; Group 2: n=15, 38.5%; p=.08). Twenty patients (26.7%) never became pregnant. Age at the time of surgery (OR=0.86; 95% CI=0.78-0.96, p=.002) and duration of infertility (OR=0.80; 95% CI=0.69-0.92, p=.006) were identified as independent indicators for pregnancy. CONCLUSION CO2 laser-treated endometrioma is associated with pregnancy rates equal to those observed after cystectomy and favorable IVF outcomes. The one step CO2 fiber laser techinique may represent a viable alternative to cystectomy.

  • Ovarian responsiveness in assisted reproductive technology after CO2 fiber laser vaporization for endometrioma treatment: preliminary data
    Jessica OTTOLINA, Stefano FERRARI, Ludovica BARTIROMO, Giulia BONAVINA, Noemi SALMERI, Matteo SCHIMBERNI, Sofia MAKIEVA, Iacopo TANDOI, Enrico PAPALEO, Paola VIGANÒ,et al.

    Edizioni Minerva Medica
    BACKGROUND Data about endometrioma ablation using energies with little thermal spread reported good results in terms of ovarian reserve and postoperative pregnancy rates. The aim of the present study was to assess the impact of 'one step' CO2 fiber laser vaporization for endometrioma on subsequent controlled ovarian stimulation. METHODS This prospective observational cohort study included a consecutive series of infertile patients who have undergone CO2 fiber laser vaporization for endometrioma treatment. The primary endpoint was to assess the number of follicles per ovary growing during controlled ovarian stimulation. The secondary endpoints included the number of oocytes retrieved, the total number of embryos obtained and the cumulative clinical pregnancy rate per patient treated. RESULTS Twenty-six patients underwent assisted reproductive technology after surgery for endometriosis-related infertility. In unilateral operated ovaries at the end of controlled ovarian stimulation no significant differences emerged from comparison of total recruited follicles in the operated ovary and in the contralateral ovary (p=0.55). If considering only bilateral endometriomas, the number of recruited follicles at the end of controlled ovarian stimulation was similar in both operated ovaries (p=0.79). The number of cumulative clinical pregnancies was 15 (57.7%; 95% CI: 38.5-76.9 %). When comparing women aged ≤ 35 years to those aged > 35 years, controlled ovarian stimulation outcomes were significantly higher in the younger patients. Age at the time of assisted reproductive technology was the only independent predictor for follicular growth during ovarian hyperstimulation (CI: -1.27 to -0.116, p=0.027). CONCLUSIONS CO2 laser-treated endometrioma is associated with favorable reproductive assisted reproductive technology outcomes.

  • Delaying surgery for patients with a previous SARS-CoV-2 infection
    C. Collaborative

    Oxford University Press (OUP)
    With at least 28 elective million operations delayed during the first three months of the COVID-19 pandemic, the number of patients who will require surgery after a previous SARS-CoV-2 infection is likely to increase rapidly1. Operating on patients with an active perioperative SARS-CoV-2 infection is now known to carry a very high pulmonary complication and mortality rate2. Urgent information is needed to guide whether postponing surgery in patients with a previous SARS-CoV-2 infection leads to a clinical benefit, and the optimal length of delay.

  • Maternal arsenic exposure and gestational diabetes: A systematic review and meta-analysis
    Noemi Salmeri, Roberta Villanacci, Jessica Ottolina, Ludovica Bartiromo, Paolo Cavoretto, Carolina Dolci, Rosalba Lembo, Matteo Schimberni, Luca Valsecchi, Paola Viganò,et al.

    MDPI AG
    Gestational diabetes mellitus (GDM) is a metabolic complication associated with adverse outcomes for mother and fetus. Arsenic (As) exposure has been suggested as a possible risk factor for its development. The aim of this meta-analysis was to provide a comprehensive overview of published evidence on the association between As and GDM. The systematic search from PubMed, MEDLINE, and Scopus was limited to full-length manuscripts published in peer-reviewed journals up to April 2020, identifying fifty articles. Ten studies met the inclusion criteria, nine for quantitative synthesis with a total of n = 1984 GDM cases. The overall pooled risk was 1.56 (95% Confidence Interval - CI = 1.23, 1.99) with moderate heterogeneity (χ2 = 21.95; I2% = 64). Several differences among the included studies that may account for heterogeneity were investigated. Stratification for exposure indicator confirmed a positive association for studies assessing urine As. A slightly higher risk was detected pooling studies based in Asia rather than in North America. Stratification for GDM diagnostic criteria showed higher risks when diagnosis was made according to the Canadian Diabetes Association (CDA-SOGC) or World Health Organization (WHO) criteria, whereas a lower risk was observed when adopting the American Diabetes Association (ADA) criteria. These results provide additional evidence for a possible association between As exposure and GDM, although the data need to be interpreted with caution due to heterogeneity.

  • Pathogenesis of bowel endometriosis
    Jessica Ottolina, Ludovica Bartiromo, Matteo Schimberni, Paola Viganò, and Massimo Candiani

    Springer International Publishing

  • Assessment of coagulation parameters in women affected by endometriosis: Validation study and systematic review of the literature
    Jessica Ottolina, Ludovica Bartiromo, Carolina Dolci, Noemi Salmeri, Matteo Schimberni, Roberta Villanacci, Paola Viganò, and Massimo Candiani

    MDPI AG
    The presence of endometriosis determines an inflammatory response locally. The objective of this validation study and systematic review was to assess systemic levels of coagulation and inflammatory parameters in women with or without the disease. We conducted a retrospective analysis of a database prospectively collected from January 2017 to February 2020 including n = 572 women who underwent laparoscopic surgery for endometriosis (cases, n = 324) or other benign gynecologic diseases (controls, n = 248). Inflammatory markers and coagulation parameters were determined. An advanced systematic search of the literature on the same parameters was conducted up to April 2020. A significantly higher neutrophil count was found in endometriosis patients. Patients with endometriomas and stage III–IV disease had a significantly lower absolute lymphocyte count and shortened activated partial thromboplastin time (aPTT) values. In the final regression model, aPTT retained significant predictive value for stage III–IV endometriosis (odds ratio (OR) = 0.002, 95% confidence interval (CI) = 0.00–0.445; p = 0.024). Results from the n = 14 included studies in the systematic review are characterized by a high variability, but some consistency has been found for alterations in thrombin time, platelet-to-lymphocyte ratio, and neutrophil count associated with endometriosis. Modest systemic changes of some inflammatory and coagulation parameters are associated with endometriosis. Indeed, all the modifications detected are still within the normal reference intervals, explaining the high heterogeneity among studies.

  • Early-life factors, in-utero exposures and endometriosis risk: a meta-analysis
    Jessica Ottolina, Matteo Schimberni, Sofia Makieva, Ludovica Bartiromo, Teresa Fazia, Luisa Bernardinelli, Paola Viganò, Massimo Candiani, and Davide Gentilini

    Elsevier BV
    This meta-analysis aimed to offer a general picture of the available data on the effects of early-life factors on the risk of developing endometriosis in adult life. An advanced, systematic search of the online medical databases PubMed, EMBASE and CINAHL was limited to full-length manuscripts published in English in peer-reviewed journals up to February 2019. Log of relative risk (RR) was employed to calculate the pooled effect sizes using both fixed and random effects modelling and I-squared tests to assess heterogeneity. Funnel plots were used to investigation publication bias. The meta-analysis was registered in PROSPERO (ID CRD42019138668). Six studies that included a total of 2360 women affected by endometriosis were analysed. The pooled results showed that the risk of developing endometriosis in adult life was significantly increased by being born prematurely (logRR 0.21, 95% CI -0.03 to 0.40), having a low birthweight (logRR 0.35, 95% CI -0.15 to 0.54), being formula-fed (logRR 0.65, 95% CI -0.35 to 0.95) and having been exposed to diethylstilbestrol (DES) in utero (logRR 0.65, 95% CI 0.26 to 1.04. Among intrauterine and early neonatal exposures, prematurity, birthweight, formula feeding and DES were risk factors for the development of endometriosis in adult life.

  • Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study
    Dmitri Nepogodiev, Aneel Bhangu, James C Glasbey, Elizabeth Li, Omar M Omar, Joana FF Simoes, Tom EF Abbott, Osaid Alser, Alexis P Arnaud, Brittany K Bankhead-Kendall,et al.

    Elsevier BV
    Summary Background The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 82·6% (219 of 265) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p<0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p<0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p<0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.