Publications by authors named "Stefano Palomba"

207 Publications

Linzagolix: a new GnRH-antagonist under investigation for the treatment of endometriosis and uterine myomas.

Expert Opin Investig Drugs 2021 Jul 18. Epub 2021 Jul 18.

Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genova, Italy.

Introduction: : Uterine myomas and endometriosis are painful, benign hormone-dependent diseases affecting women of reproductive age. Substantial efforts have been made to develop innovative medical options for treating these gynecologic diseases. Elagolix and relugolix have been approved in some countries for treating endometriosis and uterine myomas, respectively; however, linzagolix (OBE 2109, KLH 2109) is a new oral gonadotropin-releasing hormone (GnRH) antagonist in phase II-III trials. Treatment options for women with contraindications for certain hormonal therapies or who refuse particular options, are the driving force behind the development of new drugs in this area.

Area Covered: This drug evaluation highlights definitive and preliminary results from previous and ongoing studies of linzagolix for the treatment of endometriosis and uterine myomas.

Expert Opinion: Linzagolix showed a dose-dependent and rapidly reversible action on the pituitary-gonadal axis. In a recent phase II trial (EDELWEISS), linzagolix significantly reduced pain related to endometriosis and improved quality of life at single daily doses of 75-200 mg. The preliminary results of international, double-blind phase III trials (PRIMROSE 1 and 2) reported its efficacy in treating heavy menstrual bleeding related to uterine myomas with a good safety profile. Further studies will determine the necessity of add-back therapy during long-term use of linzagolix.
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http://dx.doi.org/10.1080/13543784.2021.1957830DOI Listing
July 2021

Endometrial function in women with polycystic ovary syndrome: a comprehensive review.

Hum Reprod Update 2021 Apr;27(3):584-618

Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA.

Background: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. An endometrial component has been suggested to contribute to subfertility and poor reproductive outcomes in affected women.

Objective And Rationale: The aim of this review was to determine whether there is sufficient evidence to support that endometrial function is altered in women with PCOS, whether clinical features of PCOS affect the endometrium, and whether there are evidence-based interventions to improve endometrial dysfunction in PCOS women.

Search Methods: An extensive literature search was performed from 1970 up to July 2020 using PubMed and Web of Science without language restriction. The search included all titles and abstracts assessing a relationship between PCOS and endometrial function, the role played by clinical and biochemical/hormonal factors related to PCOS and endometrial function, and the potential interventions aimed to improve endometrial function in women with PCOS. All published papers were included if considered relevant. Studies having a specific topic/hypothesis regarding endometrial cancer/hyperplasia in women with PCOS were excluded from the analysis.

Outcomes: Experimental and clinical data suggest that the endometrium differs in women with PCOS when compared to healthy controls. Clinical characteristics related to the syndrome, alone and/or in combination, may contribute to dysregulation of endometrial expression of sex hormone receptors and co-receptors, increase endometrial insulin-resistance with impaired glucose transport and utilization, and result in chronic low-grade inflammation, immune dysfunction, altered uterine vascularity, abnormal endometrial gene expression and cellular abnormalities in women with PCOS. Among several interventions to improve endometrial function in women with PCOS, to date, only lifestyle modification, metformin and bariatric surgery have the highest scientific evidence for clinical benefit.

Wider Implications: Endometrial dysfunction and abnormal trophoblast invasion and placentation in PCOS women can predispose to miscarriage and pregnancy complications. Thus, patients and their health care providers should advise about these risks. Although currently no intervention can be universally recommended to reverse endometrial dysfunction in PCOS women, lifestyle modifications and metformin may improve underlying endometrial dysfunction and pregnancy outcomes in obese and/or insulin resistant patients. Bariatric surgery has shown its efficacy in severely obese PCOS patients, but a careful evaluation of the benefit/risk ratio is warranted. Large scale randomized controlled clinical trials should address these possibilities.
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http://dx.doi.org/10.1093/humupd/dmaa051DOI Listing
April 2021

Modular nonlinear hybrid plasmonic circuit.

Nat Commun 2020 May 15;11(1):2413. Epub 2020 May 15.

Institute of Photonics and Optical Science, School of Physics, The University of Sydney, Sydney, NSW, 2006, Australia.

Photonic integrated circuits (PICs) are revolutionizing nanotechnology, with far-reaching applications in telecommunications, molecular sensing, and quantum information. PIC designs rely on mature nanofabrication processes and readily available and optimised photonic components (gratings, splitters, couplers). Hybrid plasmonic elements can enhance PIC functionality (e.g., wavelength-scale polarization rotation, nanoscale optical volumes, and enhanced nonlinearities), but most PIC-compatible designs use single plasmonic elements, with more complex circuits typically requiring ab initio designs. Here we demonstrate a modular approach to post-processes off-the-shelf silicon-on-insulator (SOI) waveguides into hybrid plasmonic integrated circuits. These consist of a plasmonic rotator and a nanofocusser, which generate the second harmonic frequency of the incoming light. We characterize each component's performance on the SOI waveguide, experimentally demonstrating intensity enhancements of more than 200 in an inferred mode area of 100 nm, at a pump wavelength of 1320 nm. This modular approach to plasmonic circuitry makes the applications of this technology more practical.
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http://dx.doi.org/10.1038/s41467-020-16190-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229200PMC
May 2020

Uterine transplantation and IVF for congenital or acquired uterine factor infertility: A systematic review of safety and efficacy outcomes in the first 52 recipients.

PLoS One 2020 29;15(4):e0232323. Epub 2020 Apr 29.

Department of Obstetrics & Gynaecology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

Uterine transplantation (UTx) associated with IVF restores fertility in women affected by absolute uterine factor infertility (AUFI). Pregnancies achieved both in women undergoing any solid organ transplantation and following IVF are associated with an increased risk of maternal and neonatal complications. This systematic review evaluated this risk in UTx-IVF treated women focusing on the safety and efficacy features of the treatment. Twenty-two studies and three press releases reporting on 52 UTx-IVF treatments were identified. Regarding the safety of treatment, 38/52 (73,1%) of surgical procedures led to the restoration of uterine function in recipients, 12/52 (23,1%) of recipients experienced post-operative complications requiring hysterectomy, and 2/52 (3,8%) of procedures failed before uterine recipients' surgery due to intra-operative complications. Regarding the efficacy of treatment, results focused on transplanted patients showing full recovery of organ functioning: 16/38 (42,1%) of patients achieved a pregnancy, including two women who gave births twice. UTx-IVF pregnancies led to 16 deliveries and all new-borns were healthy. Six out of 16 (37,5%) UTx pregnancies faced major complications during gestation. Preterm births occurred in 10/16 (62,5%) UTx deliveries. Our data indicates that the risk of gestational and delivery complications deserves important consideration in AUFI women receiving UTx-IVF treatments. However, these observations are preliminary and need to be revised after larger series of data are published.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232323PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190173PMC
July 2020

First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis.

Hum Reprod Update 2019 11;25(6):717-732

Robinson Research Institute and Adelaide Medical School, University of Adelaide, North Adelaide, SA, Australia.

Background: Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment-covariate interaction analyses and therefore offers an opportunity for personalised medicine.

Objective And Rationale: We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics.

Search Methods: We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs.

Outcomes: IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17-1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23-1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38-2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01-1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00-1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00-1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87-1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01-1.06).

Wider Implications: In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS.
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http://dx.doi.org/10.1093/humupd/dmz029DOI Listing
November 2019

Uterine Papillary Serous Carcinoma Arising in a Polyp: A Multicenter Retrospective Analysis on 75 Patients.

Am J Clin Oncol 2019 05;42(5):472-480

Unit of Obstetrics and Gynecology, Azienda USL-IRCCS of Reggio Emilia.

Objectives: The objectives of this study were to evaluate whether the international recommendations on the management of uterine papillary serous carcinoma arising in a polyp are uniformly followed in Italian Oncologic Centers and whether the strategy adopted is effective.

Materials And Methods: Patients with uterine papillary serous carcinoma arising in a polyp and who had undergone a hysterectomy were identified in the 2003-2013 database of 7 Italian Gynecologic Oncology Centers. Clinical and pathologic characteristics and outcomes were compared between staging procedure types. Survival curves of the women were plotted using the Kaplan-Meier method and analyzed using Cox regression hazard model and the log-rank test. Associations between clinical parameters and the incidence of recurrence were assessed by generalized linear models and the Fisher test.

Results: A total of 75 patients met the inclusion criteria. Recurrence-free survival was affected positively by type of surgical staging and negatively by preoperative diagnosis of hypertension. The association between surgical staging and recurrence-free survival resulted significant at univariate survival analysis (P=0.048 and 0.045) and maintained a trend of significance (P=0.070) in multivariate analysis, whereas hypertension was demonstrated to be the principal influencing factor.

Conclusions: The international recommendations on the management of uterine papillary serous carcinoma are not uniformly followed in daily practice, although the extension of the surgery seems to be associated with lower recurrence rates also when uterine papillary serous carcinoma is confined to a polyp or endometrial surface.
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http://dx.doi.org/10.1097/COC.0000000000000541DOI Listing
May 2019

Changes in visual function and ocular morphology in women who have undergone ART treatment and children born as a result of ART treatment: a systematic review.

Reprod Biomed Online 2019 Apr 7;38(4):621-633. Epub 2018 Dec 7.

Department of Gynaecology and Obstetrics, Grande Ospedale Metropolitano of Reggio Calabria, Reggio Calabria, Italy. Electronic address:

As all the structures of the human eye are characterized by sex hormone receptors, this study tested the hypothesis that assisted reproductive technology (ART) treatment influences visual function and ocular morphology in women who have undergone ART treatment and children born as a result of ART treatment. A systematic literature search of all original articles published up to August 2018 was performed using the PubMed database, including all original studies available in the literature. Review articles, studies in which participants underwent mixed interventions (i.e. other than ART treatment), studies reporting data on ocular malformations in ART offspring, and studies written in languages other than English were excluded. All selected articles were analysed to assess the level of evidence according to the Oxford Centre for Evidence-Based Medicine 2011 guidelines, and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation system. Although sparse data suggest that ART treatment can influence visual function and ocular morphology in women who have undergone ART treatment and children born as a result of ART treatment, the available evidence is inconclusive given its low level and quality. More high-quality research is needed to assess the potential interaction between ART treatment and the eye.
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http://dx.doi.org/10.1016/j.rbmo.2018.11.007DOI Listing
April 2019

Radiations and female fertility.

Reprod Biol Endocrinol 2018 Dec 16;16(1):112. Epub 2018 Dec 16.

Department of Medical and Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Faculty of Medicine and Psychology, University of Rome "Sapienza", Rome, Italy.

Hundreds of thousands of young women are diagnosed with cancer each year, and due to recent advances in screening programs, diagnostic methods and treatment options, survival rates have significantly improved. Radiation therapy plays an important role in cancer treatment and in some cases it constitutes the first therapy proposed to the patient. However, ionizing radiations have a gonadotoxic action with long-term effects that include ovarian insufficiency, pubertal arrest and subsequent infertility. Cranial irradiation may lead to disruption of the hypothalamic-pituitary-gonadal axis, with consequent dysregulation of the normal hormonal secretion. The uterus might be damaged by radiotherapy, as well. In fact, exposure to radiation during childhood leads to altered uterine vascularization, decreased uterine volume and elasticity, myometrial fibrosis and necrosis, endometrial atrophy and insufficiency. As radiations have a relevant impact on reproductive potential, fertility preservation procedures should be carried out before and/or during anticancer treatments. Fertility preservation strategies have been employed for some years now and have recently been diversified thanks to advances in reproductive biology. Aim of this paper is to give an overview of the various effects of radiotherapy on female reproductive function and to describe the current fertility preservation options.
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http://dx.doi.org/10.1186/s12958-018-0432-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295315PMC
December 2018

Lifestyle and fertility: the influence of stress and quality of life on female fertility.

Reprod Biol Endocrinol 2018 Dec 2;16(1):113. Epub 2018 Dec 2.

Center of Reproductive Medicine and Surgery, Arcispedale Santa Maria Nuova (ASMN) - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Reggio Emilia, Italy.

There is growing evidence that lifestyle choices account for the overall quality of health and life (QoL) reflecting many potential lifestyle risks widely associated with alterations of the reproductive function up to the infertility. This review aims to summarize in a critical fashion the current knowledge about the potential effects of stress and QoL on female reproductive function. A specific literature search up to August 2017 was performed in IBSS, SocINDEX, Institute for Scientific Information, PubMed, Web of Science and Google Scholar. Current review highlights a close relationship in women between stress, QoL and reproductive function, that this association is more likely reported in infertile rather than fertile women, and that a vicious circle makes them to have supported each other. However, a precise cause-effect relationship is still difficult to demonstrate due to conflicting results and the lack of objective measures/instruments of evaluation.
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http://dx.doi.org/10.1186/s12958-018-0434-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275085PMC
December 2018

A theory of waveguide design for plasmonic nanolasers.

Nanoscale 2018 Dec 14;10(45):21434-21440. Epub 2018 Nov 14.

Institute of Photonics and Optical Science (IPOS), School of Physics, The University of Sydney, NSW 2006, Australia.

We propose a theory for the waveguide design and analysis for plasmonic nanolasers by reformulating the fundamental waveguide requirements. This theory does not rely on further optimizing previously used structures, but examines each possible design without prejudice. Our exploration of one-dimensional (i.e., layered) plasmonic nanowaveguide geometries and the subsequent extension to 2D structures not only provides a deep understanding of the characteristics of currently used designs, but also leads to superior structures with the potential to address long-standing challenges in plasmonic nanolasers. In addition, we discover analogies between the reformulated fundamental requirements for the waveguide for nanolasers and nanoscale four-wave mixing (FWM) devices. Therefore, after a slight modification, our theory can also be applied to the waveguide design for plasmonic FWM devices.
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http://dx.doi.org/10.1039/c8nr04898cDOI Listing
December 2018

Pregnancy complications in infertile patients with polycystic ovary syndrome: updated evidence.

Minerva Ginecol 2018 Dec 11;70(6):754-760. Epub 2018 Apr 11.

Department of Obstetrics and Gynecology, Local Health Unit and Institute for Research and Care of Reggio Emilia, Reggio Emilia, Italy.

Polycystic ovary syndrome (PCOS) is a common female disorder with a pathogenesis still today not completely known. To the present, PCOS is considered more than just a reproductive disorder since several metabolic consequences that could affect women's health during different stages of reproductive and post-reproductive life were reported. The aim of the current review was to evaluate present evidence-based data regarding the pregnancy complications in infertile patients with PCOS. An extensive literature search until February 2018 was performed in PubMed, Medline, the Cochrane Library and Web of Science. Outcomes were classified in: early pregnancy complications, late pregnancy complications, perinatal complications, offspring health and long-term offspring and maternal health. Even if the exact mechanisms involved are still unclear, women with PCOS have an increased risk of pregnancy-related complications, such as gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preeclampsia (PE), premature delivery and caesarean section. Moreover, the offspring of women with PCOS are also at increased risk of congenital anomalies and hospitalization in childhood. Further studies are needed to study the mechanism underlying pregnancy complications in PCOS and to identify any interventions to reduce the risk of obstetric and neonatal risks in women affected by PCOS and in their offspring.
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http://dx.doi.org/10.23736/S0026-4784.18.04230-2DOI Listing
December 2018

Reference intervals for hemoglobin and hematocrit in a low-risk pregnancy cohort: implications of racial differences.

J Matern Fetal Neonatal Med 2019 Sep 23;32(17):2897-2904. Epub 2018 Mar 23.

b Department of Obstetrics and Gynecology , Arcispedale Santa Maria Nuova - IRCCS , Reggio Emilia , Italy.

As anemia in pregnancy is associated with adverse perinatal outcomes, we sought to define the mean and the fifth percentile of Hb and Ht using a contemporary multiethnic large cohort of low-risk pregnancies, and assess potential racial differences. We conducted a retrospective cohort study on women who delivered between 1 January 2008 and 31 December 2013 in Reggio Emilia County, Italy. Linear mixed effects models were used to describe changes in mean Hb and Ht, while quantile regression with matrix-design bootstrap defined changes in the fifth percentile of Hb and Ht, controlling for race, maternal age, smoking, and pregnancy number. We analyzed 23,657 hemograms from 7318 pregnancies and 6870 women. Multivariate analysis showed that when compared to Caucasians', African women's mean Hb and Ht were respectively 0.24 (95%CI 0.3-0.17) g/dl and 0.7 (95%CI 0.8-0.5) % lower, while Asian mothers' were 0.11 (95%CI 0.19-0.03) g/dl and 0.3 (95%CI 0.5-0.1) % inferior. Similarly, both African and Asian women had lower fifth Ht percentiles (-1, 95%CI -1.3 to -0.6, and -0.4, 95%CI -0.7 to -0.04) than Caucasians, while African mothers also had lower fifth Hb percentile (0.3, 95%CI 0.5-0.1). The fifth percentile for Hb and Ht were, respectively, 11.3 (95%CI 11-11.5) g/dl and 32.8 (95%CI 32.3-33.4) % in the first trimester, 10.4 (95%CI 10.1-10.6) g/dl and 30.2 (95%CI 29.6-30.8) % in the second trimester, 10.1 (95%CI 9.8-10.3) g/dl and 30.6 (95%CI 30-31.1) % in the third trimester. We provided contemporary references to define anemia in pregnancy, and we confirmed that even in pregnancy, African and Asian women have lower Hb and Ht than Caucasian. Racial and population-specific references may have significant clinical and public health implication for more accurate disease diagnosis and appropriate treatment.
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http://dx.doi.org/10.1080/14767058.2018.1452905DOI Listing
September 2019

Food restriction during pregnancy and female offspring fertility: adverse effects of reprogrammed reproductive lifespan.

J Ovarian Res 2017 Dec 28;10(1):77. Epub 2017 Dec 28.

Unit of Gynecology and Obstetrics, Grande Ospedale Metropolitano "Bianchi - Melacrino - Morelli", Reggio Calabria, Italy.

Background: Food restriction during pregnancy can influence the health of the offspring during the adulthood. The aim of the present study was to examine the effect of maternal food restriction (MFR) on the reproductive performance in female rat offspring from the first (FR1) and second (FR2) generations.

Methods: Adult virgin Wistar female rats were given free access to tap water and were fed ad libitum on standard rodent chow, were mated with virgin adult males, and then were randomly divided into two groups: controls (that was fed ad libitum ) and food-restricted group (FR, that was given only 50% of ad libitum food throughout gestation). Their first (FR1) and the second (FR2) generation of offspring were fed ad libitum and sacrificed before puberty and at adulthood. Their ovaries were removed and their histology evaluated by estimating the number of follicles (total and at various stages of folliculogenesis), and the presence of multi-nuclei oocytes and multi-oocyte follicles.

Results: Total number of ovarian follicles was lower in FR1 females at week 4 in comparison with controls, while it was not different in FR2 females vs.

Controls: The number of the primordial follicle was lower in FR1 and FR2 females vs. controls at both week 4 and at week 8. When compared to the controls, the follicles containing multi-nuclei oocytes were more frequent in ovaries from FR1 and FR2 females at week 4, and higher and lower respectively in ovaries form FR1 and FR2 females at week 8.

Conclusion: MFR affects ovarian histology by inducing the development of abnormal follicles in the ovaries in first and second generation offspring. This finding could influence the ovarian function resulting in an early pubertal onset and an early decline in reproductive lifespan.
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http://dx.doi.org/10.1186/s13048-017-0372-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745764PMC
December 2017

Obstetric and perinatal outcomes in subfertile patients who conceived following low technology interventions for fertility enhancement: a comprehensive review.

Arch Gynecol Obstet 2018 01 29;297(1):33-47. Epub 2017 Oct 29.

Division of Maternal-Fetal Medicine, Utah University, Salt Lake City, UT, USA.

Purpose: Low technology interventions for fertility enhancement (LTIFE) are strategies that avoid retrieval, handling, and manipulation of female gametes. The definition of LTIFE is yet to be widely accepted and clarified, but they are commonly used in milder cases of infertility and subfertility. Based on these considerations, the aim of the present study was comprehensively to review and investigate the obstetric and perinatal outcomes in subfertile patients who underwent LTIFE.

Methods: A literature search up to May 2017 was performed in IBSS, SocINDEX, Institute for Scientific Information, PubMed, Web of Science, and Google Scholar. An evidence-based hierarchy was used according to The Oxford Centre for Evidence-Based Medicine to determine which articles to include and analyze, and to provide a level of evidence of each association between intervention and outcome.

Results: This analysis identified preliminary and low-grade evidence on the influence of LTIFE on obstetric and perinatal outcomes in subfertile women.

Conclusions: LTIFE women should deserve major consideration from Clinicians/Researchers of Reproductive Medicine, because these treatments could be potentially responsible for mothers' and babies' complications. So far, the lack of well-designed and unbiased studies makes further conclusions difficult to be drawn.
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http://dx.doi.org/10.1007/s00404-017-4572-9DOI Listing
January 2018

Fano enhancement in hybrid plasmonic nanoresonator.

Opt Express 2017 Aug;25(17):20034-20044

Combining the advantages of photonics (low loss) and plasmonics (high field confinement), while mitigating their respective drawbacks, can greatly enhance the light-matter interaction efficiency. Here we make use of a time-dependent coupled mode theory in order to theoretically model the excitation of a plasmonic nanoantenna via a photonic resonator. We show that including the light source-nanoantenna direct coupling substantially enhances the overall coupling efficiency, maintaining the same input power.
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http://dx.doi.org/10.1364/OE.25.020034DOI Listing
August 2017

Assisted reproductive technology treatments and quality of life: a longitudinal study among subfertile women and men.

J Assist Reprod Genet 2017 Oct 21;34(10):1307-1315. Epub 2017 Jul 21.

Unit of Obstetrics and Gynecology, IRCCS - ASMN of Reggio Emilia, Reggio Emilia, Italy.

Purpose: Quality of life (QoL) may represent a comprehensive indicator for the assessment of the psychological impact of complex clinical conditions, such as infertility. Infertile women have a worse QoL compared to both infertile men and non-infertile controls. However, the initial phases of infertility treatments have been frequently investigated using cross-sectional study designs. This prospective longitudinal study aimed at assessing the health-related QoL change across different phases of assisted reproductive technology (ART) treatments in subfertile women and men.

Methods: Eighty-five subfertile women and men undergoing ART cycles were assessed at the beginning of the ovarian stimulation, during oocyte retrieval before discharging, and around 14 days after the embryo transfer. QoL was assessed through the Short Form 36.

Results: Irrespective of the cause of infertility, work status, and age, QoL levels decreased from the first to the third assessment, and women scored significantly lower than men to each QoL indicator. Additionally, a higher number of previous ART failures had a negative impact on QoL, irrespective of gender and the phase of treatment. ART outcome marginally affected women's QoL across time.

Conclusion: Infertile women have a worse QoL throughout all phases of ARTs compared to men, and this difference increases in infertile patients with more than one previous ART failure.
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http://dx.doi.org/10.1007/s10815-017-1000-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633563PMC
October 2017

Effect of the previous reproductive outcomes in subfertile women after in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) treatments on perinatal anxious and depressive symptomatology.

J Psychosom Obstet Gynaecol 2018 03 21;39(1):29-37. Epub 2017 Feb 21.

b Unit of Obstetrics & Gynecology , IRCCS - ASMN of Reggio Emilia , Reggio Emilia , Italy.

Introduction: The present study aims to investigate the effects of previous reproductive outcomes on the levels of depression, anxiety and perceived social support in subfertile women who conceived after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment.

Methods: A prospective cohort study was developed. Data were collected on subfertile patients who conceived after IVF/ICSI treatment. All demographic and clinical data were recorded. The Edinburgh Postnatal Depression Scale, the State-Trait Anxiety Inventory-Y and the Multidimensional Scale of Perceived Social Support at 22 and 32 weeks of gestation and 15 days after delivery were completed. Data were analyzed comparing patients who conceived at their first IVF/ICSI cycle, after one unsuccessful ARTs cycle, and after multiple unsuccessful IVF/ICSI cycles.

Results: A significant increase in state anxiety and depression scores from 22 gestational weeks of gestation to 15 days after delivery was observed in patients who received multiple unsuccessful IVF/ICSI cycles compared with other groups. No significant difference in perceived social support was detected among groups. The differences in depression and anxiety scores remained consistent after controlling for perceived social support.

Discussion: A history of unsuccessful IVF/ICSI treatments seems to leave women more vulnerable in facing the duties of the new parental role. Such possibility underlies the importance of the availability of a psychological support for these women, even after a successful medical treatment for infertility.
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http://dx.doi.org/10.1080/0167482X.2017.1286474DOI Listing
March 2018

The Distribution of Stroma and Antral Follicles Differs between Insulin-Resistance and Hyperandrogenism-Related Polycystic Ovarian Syndrome.

Front Endocrinol (Lausanne) 2017 31;8:117. Epub 2017 May 31.

Department of Obstetrics and Gynecology, Policlinico Universitario Duilio Casula, University of Cagliari, Cagliari, Italy.

Introduction: Although insulin resistance plays an important pathogenetic role in polycystic ovary syndrome (PCOS), no correlation between ultrasound PCOS pattern and insulin resistance has yet been reported. The aim of this retrospective observational study was to assess whether the ovarian ultrasonographic parameter differed between PCOS women with insulin resistance and those with a hyperandrogenic profile.

Materials And Methods: Women who fulfilled the Rotterdam criteria for PCOS were retrospectively studied. Anthropometric, biochemical, and clinical data were recorded. Women were divided into two groups based on specific transvaginal ultrasound parameters: subjects with more than half of the follicles measuring between 5 and 9 mm in diameter, an ultrasonographic determined stroma/total area (S/A) > 0.34 and a "necklace" sign of antral follicles (Group A); and subjects with more than half of the antral follicles measuring between 2 and 4 mm in diameter, an S/A ≤ 0.34; no "necklace" sign but ubiquitously distributed follicles determined by ultrasound (Group B). The association between these ultrasound patterns and the presence of insulin resistance was also evaluated.

Results: Seventy-eight patients were enrolled: 33 with ultrasound sound pattern A and 45 with pattern B. The latter pattern had a sensitivity of 88% and a specificity of 78% in predicting PCOS women with insulin resistance. There were no differences in age, Ferriman-Gallwey score, and serum gonadotropin or androgen levels between the two groups. Body mass index, the waist-to-hip ratio, and homeostasis model assessment were significantly higher in group B than in group A ( < 0.05). Conversely, sex hormone binding globulin levels and ovarian volume were significantly higher in group A ( < 0.05). Insulin resistance was more frequent in group B than in group A (36/41, 87.8% versus 7/32, 21.8%;  < 0.05).

Conclusion: These results suggest that insulin resistance could be associated with a specific ultrasound pattern in PCOS patients.
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http://dx.doi.org/10.3389/fendo.2017.00117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449504PMC
May 2017

General analytic expression and numerical approach for the Kerr nonlinear coefficient of optical waveguides.

Opt Lett 2017 Apr;42(7):1329-1332

The Kerr nonlinear coefficient γ is a key parameter that quantifies the nonlinear strength of an optical waveguide. For lossy waveguides such as plasmonic waveguides, the literature is confusing because various expressions derived by different groups have generally not been validated, and the conditions when they apply are not explicitly specified. Here we derive a rigorous and full-vectorial model, leading to both a general analytic expression and a general numerical approach for finding γ, as well as to their underlying relationship. Our results, exemplified by lossless and lossy waveguides, are consistent not only with each other, but also with the results in literature under appropriate limiting conditions. This work provides a benchmarked framework to understand and engineer nonlinear nanophotonic devices.
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http://dx.doi.org/10.1364/OL.42.001329DOI Listing
April 2017

The effect of a uterine manipulator on the recurrence and mortality of endometrial cancer: a multi-centric study by the Italian Society of Gynecological Endoscopy.

Am J Obstet Gynecol 2017 06 29;216(6):592.e1-592.e11. Epub 2017 Jan 29.

Department of Obstetrics and Gynecology, University of Insubria, Del Ponte Hospital, Varese, Italy.

Background: Although widely adopted, the use of a uterine manipulator during laparoscopic treatment of endometrial cancer represents a debated issue, and some authors hypothesize that it potentially may cause an increased risk of relapse, particularly at specific sites.

Objective: Our aim was to evaluate the risk and site of disease recurrence, overall survival, and disease-specific survival in women who had laparoscopic surgery with and without the use of a uterine manipulator.

Study Design: Data were reviewed from consecutive patients who had laparoscopic surgery for endometrial cancer staging in 7 Italian centers. Subjects were stratified according to whether a uterine manipulator was used during surgery; if so, the type of manipulator was identified. Multivariable analysis to correct for possible confounders and propensity score that matched the minimize selection bias were utilized. The primary outcome was the risk of disease recurrence. Secondary outcomes were disease-specific and overall survival and the site of recurrence, according to the use or no use of the uterine manipulator and to the different types of manipulators used.

Results: We included 951 patients: 579 patients in the manipulator group and 372 patients in the no manipulator group. After a median follow-up period of 46 months (range,12-163 months), the rate of recurrence was 13.5% and 11.6% in the manipulator and no manipulator groups, respectively (P=.37). Positive lymph nodes and myometrial invasion of >50% were associated independently with the risk of recurrence after adjustment for possible confounders. The use of a uterine manipulator did not affect the risk of recurrence, both at univariate (odds ratio, 1.18; 95% confidence interval, 0.80-1.77) and multivariable analysis (odds ratio, 1.00; 95% confidence interval, 0.60-1.70). Disease-free, disease-specific, and overall survivals were similar between groups. Propensity-matched analysis confirmed these findings. The site of recurrence was comparable between groups. In addition, the type of uterine manipulator and the presence or not of a balloon at the tip of the device were not associated significantly with the risk of recurrence.

Conclusion: The use of a uterine manipulator during laparoscopic surgery does not affect the risk of recurrence and has no impact on disease-specific or overall survival and on the site of recurrence in women affected by endometrial cancer.
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http://dx.doi.org/10.1016/j.ajog.2017.01.027DOI Listing
June 2017

Shedding new light on female fertility: The role of vitamin D.

Rev Endocr Metab Disord 2017 09;18(3):273-283

Department of Sports Science and Wellness, "Parthenope" University Naples, Naples, Italy.

In the last decades several studies suggested that vitamin D is involved in the modulation of the reproductive process in women due to the expression of VDR and 1α-hydroxylase in reproductive tissues such as ovary, uterus, placenta, pituitary and hypothalamus. Vitamin D has also a role in the regulation of sex hormone steroidogenesis. Increasing evidence suggests that vitamin D might have a regulatory role in polycystic ovary syndrome (PCOS)-associated symptoms, including ovulatory dysfunction, insulin resistance and hyperandrogenism. Vitamin D deficiency also has been reported to contribute to the pathogenesis of endometriosis due to its immunomodulatory and anti-inflammatory properties. Although most of the studies supported a role of vitamin D in the onset of these diseases, randomized controlled trials to assess the efficacy of vitamin D supplementation have never been performed. In this review we critically discuss the role of vitamin D in female fertility, starting from in vitro and in vivo studies, focusing our attention on the two most frequent causes of female infertility: PCOS and endometriosis.
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http://dx.doi.org/10.1007/s11154-017-9407-2DOI Listing
September 2017

Erratum to "Inositols in the Treatment of Insulin-Mediated Diseases".

Int J Endocrinol 2016 4;2016:6189820. Epub 2016 Dec 4.

Endocrinology, Department of Sports Science and Wellness, "Parthenope" University of Naples, 80133 Naples, Italy; Fertility Techniques SSD, "S. Giovanni di Dio e Ruggi d'Aragona" University Hospital, Salerno, Italy; CMSO (Centro Medico Specialistico Orio), 84127 Salerno, Italy.

[This corrects the article DOI: 10.1155/2016/3058393.].
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http://dx.doi.org/10.1155/2016/6189820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5164898PMC
December 2016

Oocyte Competence in Women with Polycystic Ovary Syndrome.

Trends Endocrinol Metab 2017 03 14;28(3):186-198. Epub 2016 Dec 14.

Unit of Gynecology and Obstetrics, IRCCS - Arcispedale Santa Maria Nuova, Viale Risorgimento 80, Reggio Emilia 42123, Italy; University of Modena and Reggio Emilia, Via Università 4, Modena 41100, Italy.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and affects fertility and pregnancy in cases of oligoanovulation. Ovulation induction is often used to treat anovulatory patients with PCOS, but many of these women fail to conceive and resort to assisted reproductive technologies. Alterations in oocyte competence (OC) are considered potential causative factors for subfertility in women with PCOS. In this review we present and critically assess all recent clinical and experimental data regarding OC in women with PCOS. Our analysis demonstrates that the contribution of OC to reproductive potential in women with PCOS varies and largely depends on the PCOS phenotype and comorbidities associated with PCOS.
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http://dx.doi.org/10.1016/j.tem.2016.11.008DOI Listing
March 2017

Prevalence of polycystic ovary morphology in a region of South Italy.

J Ultrasound 2016 Dec 12;19(4):301-302. Epub 2016 Sep 12.

Ios and Coleman Medicina Futura Medical Center, Naples, Italy.

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http://dx.doi.org/10.1007/s40477-016-0215-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126014PMC
December 2016

Risk of adverse pregnancy and perinatal outcomes after high technology infertility treatment: a comprehensive systematic review.

Reprod Biol Endocrinol 2016 Nov 4;14(1):76. Epub 2016 Nov 4.

Department of Obstetrics and Gynecology, Chaim Sheba Medical Center (Tel Hashomer), Ramat Gan, Israel.

In the literature, there is growing evidence that subfertile patients who conceived after infertility treatments have an increased risk of pregnancy and perinatal complications and this is particularly true for patients who conceived through use of high technology infertility treatments. Moreover, high technology infertility treatments include many concomitant clinical and biological risk factors. This review aims to summarize in a systematic fashion the current evidence regarding the relative effect of the different procedures for high technology infertility treatments on the risk of adverse pregnancy and perinatal outcome. A literature search up to August 2016 was performed in IBSS, SocINDEX, Institute for Scientific Information, PubMed, Web of Science and Google Scholar and an evidence-based hierarchy was used to determine which articles to include and analyze. Data on prepregnancy maternal factors, low technology interventions, specific procedures for male factor, ovarian tissue/ovary and uterus transplantation, and chromosomal abnormalities and malformations of the offspring were excluded. The available evidences were analyzed assessing the level and the quality of evidence according to the Oxford Centre for Evidence-Based Medicine guidelines and the Grading of Recommendations Assessment, Development, and Evaluation system, respectively. Current review highlights that every single procedure of high technology infertility treatments can play a crucial role in increasing the risk of pregnancy and perinatal complications. Due to the suboptimal level and quality of the current evidence, further well-designed studies are needed.
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http://dx.doi.org/10.1186/s12958-016-0211-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097409PMC
November 2016

Salpingectomy before assisted reproductive technologies: a systematic literature review.

J Ovarian Res 2016 Nov 3;9(1):74. Epub 2016 Nov 3.

Unit of Reproductive Surgery and Medicine, ASMN-IRCCS of Reggio Emilia, Reggio Emilia, Italy.

Salpingectomy is largely used in case of hydrosalpinx in infertile women scheduled for assisted reproductive technologies (ART), whereas there is no consensus on its role in absence of hydrosalpinx. The current is a systematic literature review to collate all available evidence regarding salpingectomy as fertility enhancement procedure before ART in infertile patients. Our primary endpoint was to assess the impact of the surgical procedure on ovarian reserve, and secondary outcomes were to evaluate its benefits and harms on ART outcomes. We identified 29 papers of which 16 reporting data on the impact of tubal surgery on ovarian reserve and 24 (11 previously included) on ART outcomes. Available data suggested an absence of variation in ovarian reserve markers after unilateral salpingectomy while contradictory results were reported for bilateral surgery. Considering ART outcomes, data reported a significant improvement in ongoing pregnancy/live-birth rate in treated subjects without significant reduction in ovarian response to gonadotropin stimulation. In case of tubal disease, a surgical approach based on unilateral salpingectomy may be considered safe, without negative effects on ovarian reserve and ovarian response to controlled ovarian stimulation whilst having a positive effect on pregnancy rate. Data regarding bilateral salpingectomy and ovarian reserve are conflicting. Further trials are needed to confirm both the benefits of salpingectomy before ART and the safety of bilateral salpingectomy on ovarian reserve, and to clarify the role of uni- or bilateral surgery in case of tubal blockage without hydrosalpinx.
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http://dx.doi.org/10.1186/s13048-016-0284-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094031PMC
November 2016

Inositols in the Treatment of Insulin-Mediated Diseases.

Int J Endocrinol 2016 8;2016:3058393. Epub 2016 Sep 8.

Endocrinology, Department of Sports Science and Wellness, "Parthenope" University of Naples, 80133 Naples, Italy; Fertility Techniques SSD, "S. Giovanni di Dio e Ruggi d'Aragona" University Hospital, CMSO (Centro Medico Specialistico Orio), 84131 Salerno, Italy.

A growing body of research is currently focused on the role of inositol isomers and in particular myo-inositol (MYO-INS) and D-chiroinositol (DCI) in the treatment of insulin resistance states. Both isomers have been shown to exert insulin-mimetic action and to lower postprandial glucose. Further, insulin resistance-related diseases were associated to derangements in inositol metabolism. Thus, the aim of this review is to provide current evidence on the potential benefits of inositol isomers (MYO-INS and DCI) in the treatment of disease associated to insulin resistance such as polycystic ovary syndrome (PCOS), gestational diabetes, and metabolic syndrome. Finally, molecular insights into inositol insulin-sensitizing effects will be covered focusing on the possible role of inositol glycans as insulin second messengers.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027050PMC
http://dx.doi.org/10.1155/2016/3058393DOI Listing
October 2016

Lifestyle changes in the management of adulthood and childhood obesity.

Minerva Endocrinol 2016 Dec;41(4):509-15

Department of Sport Sciences and Wellness, Parthenope University, Naples, Italy -

Adulthood and childhood obesity is rapidly becoming an epidemic problem and it has a short and long-term impact on health. Short-term consequences are mostly represented by psychological effects; in fact obese children have more chances to develop psychological or psychiatric problems than non-obese children. The main long-term effect is represented by the fact that childhood obesity continues into adulthood obesity and this results in negative effects in young adult life, since obesity increases the risk to develop morbidity and premature mortality. The obesity-related diseases are mostly represented by hypertension, type 2 diabetes, dyslipidemia, cardiovascular diseases. Medical treatment should be discouraged in childhood because of the side effects and it should be only reserved for obese children with related medical complications. Lifestyle changes should be encouraged in both adulthood and childhood obesity. This review focuses on the management of obesity both in adulthood and in childhood, paying particular attention to lifestyle changes that should be recommended.
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December 2016

Pregnancy complications in spontaneous and assisted conceptions of women with infertility and subfertility factors. A comprehensive review.

Reprod Biomed Online 2016 Nov 20;33(5):612-628. Epub 2016 Aug 20.

Division of Matenal-Fetal Medicine, Utah University, Salt Lake City, UT, USA.

In the literature, there is growing evidence that assisted reproductive techniques increase the risk of pregnancy complications in subfertile couples. Moreover, many concomitant preconception risk factors for subfertility are frequently present in the same subject and increase the risk of pregnancy complications. This review aimed to summarize in a systematic fashion the best current evidence regarding the effects of preconception maternal factors on maternal and neonatal outcomes. A literature search up to March 2016 was performed in IBSS, SocINDEX, Institute for Scientific Information, PubMed, Web of Science and Google Scholar. An evidence-based hierarchy was used to determine which articles to include and analyse. Available data show that the risk of pregnancy complications in spontaneous and assisted conceptions is likely multifactorial, and the magnitude of this risk is probably very different according specific subgroups of patients. Notwithstanding the only moderate level and quality of the available evidence, available data suggest that the presence and the treatment of specific preconception cofactors of subfertility should be always taken into account both in clinical practice and for scientific purposes.
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http://dx.doi.org/10.1016/j.rbmo.2016.08.007DOI Listing
November 2016
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