Paolo Emanuele Levi Setti - Academia.edu (original) (raw)

Papers by Paolo Emanuele Levi Setti

This study evaluates if the pandemic has influenced ART outcome in an asymptomatic infertile popu... more This study evaluates if the pandemic has influenced ART outcome in an asymptomatic infertile population treated at one of the major COVID-19 epicenters during the weeks immediately preceding the lockdown. All ART procedures during two time periods were used for comparison: November 1st, 2018 to February 28th, 2019 (non COVID-19 risk) and November 1st, 2019 to February 29th, 2020 (COVID-19 risk). We analyzed 1,749 fresh cycles (883 non COVID-19 risk and 866 COVID- 19 risk), 1,166 embryo and 63 oocytes warming cycles (538 and 37 during non COVID and 628 and 26 during COVID-19 risk respectively). Clinical pregnancies per cycle were not different: 370 (25,38%) in non COVID vs 415 (27,30%) (p=0.237) during COVID-19 risk. There were no differences in biochemical pregnancy rates 52 (3,57%) vs 38 (2,50%) (p=0.089) nor in ectopic pregnancies 4 (1,08%) vs 3 (0,72%) (p=0,594), spontaneous abortions 84 (22,70%) vs 103 (24,82%) p=0,487, intrauterine ongoing pregnancies 282 (76,22%) vs 309 (74,46...

Antioxidants

Basic scientific research on human reproduction and oxidative damage has been extensively perform... more Basic scientific research on human reproduction and oxidative damage has been extensively performed; however, a more clinical view is still lacking. As a result, exhaustive data on the influence of oxidative stress on human ovarian response and, consequently, on fertility are still lacking. This narrative review aims at summarizing the role of oxidative stress in different conditions associated to female infertility and to list some of the main antioxidant agents. A systematic literature search was performed in May 2022 to retrieve studies regarding the oxidative stress and the human ovarian response from somatic ovarian cells to oocytes damage. Only human studies were included and the authors focused their review, in particular, on clinical implications in order to define a new research perspective on the assessment of any eventual strategy to preserve women’s fertility. Thereby, the authors evaluated the contribution of DNA repair pathways in improving women’s fertility by reducin...

Antioxidants, 2021

The reduction of female fertility over time is considered as a natural consequence of ovarian agi... more The reduction of female fertility over time is considered as a natural consequence of ovarian aging. The exact mechanism underlying this process is not fully elucidated. However, it is becoming increasingly evident that qualitative and quantitative mitochondrial genome alterations might play a relevant role. The former include mitochondrial DNA (mtDNA) damage caused by oxidative stress, the accumulation of acquired mtDNA mutations, the effects of inherited mtDNA mutations, and alterations in the mitochondrial stress response mechanism. The latter refer to alterations in the oocytes, granuolosa cells, and embryonic cells mtDNA content. The present review aims to investigate the evidence about: (1) the effect of qualitative and quantitative mtDNA alterations on female fertility, paying particular attention to those with a pathophysiology characterized by a relevant role of oxidative stress; (2) the use of oocytes, granulosa cells (GCs), embryonic cells, and peripheral blood cells mtDN...

Reproductive BioMedicine Online, 2020

The COVID-19 pandemic is an unprecedented global situation. As assisted reproductive technology (... more The COVID-19 pandemic is an unprecedented global situation. As assisted reproductive technology (ART) specialists, we should be cautious, carefully monitoring the situation while contributing by sharing novel evidence to counsel our patients, both pregnant women and would-be mothers. Time to egg collection and drop-out rates are critical parameters for scheduling treatments once the curve of infections has peaked and plateaued in each country. In order to reduce the values for these two parameters, infertile patients now require even more support from their IVF team: urgent oocyte collection for oncology patients must be guaranteed, and oocyte retrievals for women of advanced maternal age and/or reduced ovarian reserve cannot be postponed indefinitely. This document represents the position of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) in outlining ART priorities during and after this emergency.

Fertility and Sterility, 2018

The simplified SART embryo scoring system is highly correlated to implantation and live birth in ... more The simplified SART embryo scoring system is highly correlated to implantation and live birth in single blastocyst transfers. Journal of assisted reproduction and genetics, 30(4), 563-567.

Frontiers in Endocrinology, 2019

The aim of the present study is to report our experience on elective women fertility preservation... more The aim of the present study is to report our experience on elective women fertility preservation before cancer treatment. Study Design: This is a single-center retrospective observational study, including all patients who underwent elective fertility preservation before oncological treatment between January 2001 and March 2019 at our Institute. Results: Of a total of 568 women who received fertility counseling, 244 (42.9%) underwent 252 oocyte retrieval cycles after controlled ovarian stimulation for cryopreservation. The majority of patients were diagnosed with breast cancer (59.9%), followed by women affected by Hodgkin's and non-Hodgkin's lymphoma (27.4%). A minority comprised patients diagnosed with other malignancies that affected soft tissues (2.8%), ovary borderline type (2.4%), digestive system (1.6%), leukemia (1.6%), uterine cervix (1.2%). The remaining 3.1% were affected by other cancer types. The mean age of the cohort was 31.3 ± 6.4 years and the mean oocyte retrieval was 13.5± 8.4. Of 11 women who returned to attempt a pregnancy, three performed two thawed cycles. We obtained four pregnancies from 24 embryo transfers (Pregnancy Rate 36.4% for couple): two miscarriages and two live births. Overall, 95.7% of oocytes are still in storage. Conclusions: A close collaboration between Cancer and Fertility Center in a tertiary care hospital is essential to provide a good health service in oncological patients. Offering fertility preservation is no longer considered optional and must be included in every therapeutic program for women who receive an oncological diagnosis in their reproductive age. Oocyte cryopreservation appears to be a good opportunity for fertility preservation. Our results, although they are obtained in a small sample, are encouraging, even if only 4.5% of patients returned to use their gametes.

Human Reproduction, 2018

Can a second round of biopsy, vitrification and chromosomal testing provide a valid diagnosis whe... more Can a second round of biopsy, vitrification and chromosomal testing provide a valid diagnosis where the first attempt fails? SUMMARY ANSWER: The risk of inconclusive chromosomal-assessment after trophectoderm biopsy was 2.5% but a further biopsy and vitrification-warming appeared not to impair the competence of euploid blastocysts. WHAT IS KNOWN ALREADY: The increasing implementation of multicell trophectoderm biopsy has significantly reduced the risk of inconclusive diagnosis after preimplantation-genetic-testing (PGT). Yet, few reports have defined the variables that influence the risk of failure or described the technical and clinical outcomes after re-biopsy. STUDY DESIGN, SIZE, DURATION: Retrospective multicenter study involving 8990 blastocyst biopsies conducted between April 2013 and September 2017 at six IVF centers but analyzed at a single genetic laboratory. A total of 206 blastocysts were successfully re-biopsied after warming and re-expansion, then re-vitrified. And 49 of these blastocysts were diagnosed euploid and used in single-embryo-transfers (SETs). Logistic regression analyses were conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 3244 PGT-for-aneuploidies (PGT-A) cycles with a freeze-all approach, vitrification and qPCR-based analysis were performed by 2687 consenting couples. DNA amplification failure (AF) or nonconcurrent data resulted in inconclusive diagnoses. In case of DNA amplification, the cellularity of the biopsy was estimated according to a previously validated method. Euploid SETs were performed. Clinical pregnancy, miscarriage, live birth rates (LBR) and perinatal outcomes were monitored. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 2.5% of trophectoderm biopsies resulted in an inconclusive diagnosis (N = 228/8990). Specifically, 2% (N = 176/8990) resulted in AF and 0.5% (N = 52/8990) in non-concurrent results. The only parameters significantly associated with inconclusive diagnoses were the IVF center and the embryo age (days) at biopsy. Among samples with successful amplification, the number of cells in the biopsy and the day of biopsy were critical to limit non-concurrent results. In total, 213 blastocysts with an

Frontiers in Endocrinology, 2019

To study the actual controlled ovarian stimulation (COS) management in women with suboptimal resp... more To study the actual controlled ovarian stimulation (COS) management in women with suboptimal response, comparing clinical outcomes to the gonadotropins consume, considering potential role of luteinizing hormone (LH) addition to follicle-stimulating hormone (FSH). Design: Monocentric, observational, retrospective, real-world, clinical trial on fresh intra-cytoplasmic sperm injection (ICSI) cycles retrieving from 1 to 9 oocytes, performed at Humanitas Fertility Center from January 1st, 2012 to December 31st, 2015. Methods: COS protocols provided gonadotropin releasing-hormone (GnRH) agonist long, flare-up, short and antagonist. Both recombinant and urinary FSH were used for COS and LH was added according to the clinical practice. ICSI outcomes considered were: gonadotropins dosages; total, mature, injected and frozen oocytes; cumulative, transferred and frozen embryos; implantation rate; pregnancy, delivery and miscarriage rates. Outcomes were compared according to the gonadotropin regimen used during COS. Results: Our cohort showed 20.8% of low responders, defined as 1-3 oocytes retrieved and 79.2% of "suboptimal" responders, defined as 4-9 oocytes retrieved. According to recent POSEIDON stratification, cycles were divided in group 1 (6.9%), 2 (19.8%), 3 (11.7%), and 4 (61.5%). The cohort was divided in 3 groups, according to the gonadotropin's regimen. Women treated with FSH plus LH showed worst prognostic factors, in terms of age, basal FSH, AMH, and AFC. This difference was evident in suboptimal responders, whereas only AMH and AFC were different among treatment groups in low responders. Although a different result, in terms of oocytes and embryos detected, major ICSI outcomes (i.e., pregnancy and delivery rates) were similar among groups of COS treatment. Outcomes were significantly different among Poseidon groups. Implantation, pregnancy and delivery rates were significantly higher in Poseidon group 1 Levi-Setti et al. Low Prognosis Women in IVF and progressively declined in other POSEIDON groups, reaching the worst percentage in group 4. Conclusions: In clinical practice, women with worst prognosis factors are generally treated with a combination of LH and FSH. Despite low prognosis women showed a reduced number of oocytes retrieved, the final ICSI outcome, in terms of pregnancy, is similarly among treatment group. This result suggests that the LH addition to FSH during COS could improve the quality of oocytes retrieved, balancing those differences that are evident at baseline.

Journal of Assisted Reproduction and Genetics, 2018

Archivio Italiano di Urologia e Andrologia, 2017

Background: antioxidants supplementation improves sperm quality, but few trials have analyzed the... more Background: antioxidants supplementation improves sperm quality, but few trials have analyzed the effects on sperm DNA fragmentation (SDF). This study compares the effectiveness of SOD-based antioxidant supplementation plus hydroxytyrosol and carnosol in reducing SDF with other antioxidants without SOD, hydroxytyrosol, and carnosol. Materials and methods: men with high SDF at baseline were selected in our clinical database. The patients taken into account had a 2-month control. SDF was measured by Sperm Chromatin Dispersion test (SCD). Untreated men were used as a control group. The remaining subjects received some oral antioxidant supplements (12 different combinations of both hydrophilic and lipophilic antioxidants), with some of them receiving nutritional support with a SOD-based antioxidant supplementation plus hydroxytyrosol and carnosol. Results: 118 men were selected for a retrospective study. Mean age 39.3 ± 5.4 years. Fifteen had no treatment, 55 were treated with a SOD-bas...

Journal of assisted reproduction and genetics, Jan 6, 2016

The etiology of maternal aging, a common cause of female factor infertility and a rate-limiting s... more The etiology of maternal aging, a common cause of female factor infertility and a rate-limiting step in vitro fertilization (IVF) success, remains still unclear. Proteomic changes responsible for the impaired successful pregnancy outcome after IVF with aged blastocysts have not been yet evaluated. The objective of this prospective study was to employ proteomic techniques and bioinformatic tools to enlight differences at the protein level in blastocoel fluid of aged and younger woman. Protein composition of human blastocoel fluid isolated by micromanipulation from 46 blastocysts of women aged <37 years (group A) and 29 of women aged ≥37 years (group B) have been identified by a shotgun proteomic approach based on high-resolution nano-liquid chromatography electrospray-ionization-tandem mass spectrometry (nLC-ESI-MS/MS) using label free for the relative quantification of their expression levels. The proteomic analysis leads to the identification and quantification of 148 proteins; ...

Journal of Assisted Reproduction and Genetics, 2016

The aim of this study was to provide a comprehensive follow-up of fetal and perinatal outcome and... more The aim of this study was to provide a comprehensive follow-up of fetal and perinatal outcome and the incidence of congenital anomalies in babies born after fresh embryo transfers compared to those conceived spontaneously in infertile couples. Methods Retrospective comparative analysis of all clinical pregnancies from fresh cleavage-stage embryo transfer cycles (IVF and ICSI) compared with infertile patients who conceived spontaneously in the same time period (control). Congenital anomalies were classified following the European Surveillance of Congenital Anomalies (EUROCAT) classification. Results A total of 2414 assisted reproductive technology (ART) pregnancies were compared to 582 spontaneous conceptions in the control infertile group representing 2306 deliveries. No significant differences were found in pregnancy outcome between the two groups (delivery rate, abortion rate, ectopic pregnancies, medical abortions for fetal anomalies, single and twins mean gestational age, and weight at delivery). A significant difference (p < 0.001) was found in the twin (21.3 vs 2.3 %) and triplet rates (2.3 vs 0 %). A total of 2351 babies were delivered in the ART group and 449 in the control group. A total of 90 babies (3.8 %) were diagnosed with a major congenital anomaly in the ART group and 15 (3.3 %) in the control group (p = ns). The overall rate of major congenital anomalies (105/2800) in ART and spontaneous pregnancies in infertile couples was significantly higher when compared to the EUROCAT 2.0 versus 3.75 % (p = 0.0002). Discussion Babies born after ART treatments and from spontaneous conception in infertile couples had rates of congenital anomalies higher than those recorded by the EUROCAT. However, the rates of anomalies were not different within the infertile population whether conceived by ART or spontaneously. These data suggest that the diagnosis of infertility in itself is the common denominator for the increase in the rates of anomalies seen in both ART and spontaneous conceptions.

Reproductive BioMedicine Online, 2016

In addition, he received a PhD degree in neuroscience physiology and biomedical engineering from ... more In addition, he received a PhD degree in neuroscience physiology and biomedical engineering from the University of Bologna and the University of California at Berkley. His post doctorate was done at the Center for Biostabilization at the University of California at Davis. He has published over 150 scientific papers in peer-reviewed journals and filed over 60 patents and is the recipient of many prizes for basic and applied research.

Journal of Fertilization: In vitro, 2012

In March 2004 the Italian Parliament enacted a Law (Law 40/2004) establishing a long list of rest... more In March 2004 the Italian Parliament enacted a Law (Law 40/2004) establishing a long list of restrictions for ART procedures. The law articles were constructed around the assumption of considering the embryo as a human being, with the same or even more rights of the woman or the couple seeking treatment for their infertility-related childless. In detail, the Law obliged to use only 3 oocytes to be fertilised and all the resulting embryos had to be transferred. Embryo freezing as well as pre implantation screening (PGS) or diagnosis (PGD) and sperm or oocytes donation were forbidden. In May 2009 the Italian Constitutional Court was called to judge parts of the Law 40 and cancelled some of the restrictions since they violated women's rights to have access to the best possible treatment with the lower health risks for both her and the future children. The Constitutional Court stated that the decision on the number of oocytes to be used for insemination, the embryos to be transferred and the embryos to be frozen were a matter of good clinical practice and under the full responsibility of the reproductive specialist. PGD and PGS remains a matter of debate because the Court was not called specifically to address this subject, although a clear opinion in favour has been expressed in previous decisions. The Constitutional Court will be called only in the future to express a judgement on gametes donation that is still forbidden. The present work reviews the clinical and social effects produced by 5 years of a restrictive ART Law (2004-2009); the preliminary results after the Italian Constitutional Court decision (May-December 2009 and comments on cross border infertility treatment for procedures that are still barred.

Reproductive biomedicine online, Jan 16, 2015

Poor responders represent a significant percentage of couples treated in IVF units (10-24%), but ... more Poor responders represent a significant percentage of couples treated in IVF units (10-24%), but the standard definition of poor responders remains uncertain and consequently optimal treatment options remain subjective and not evidence-based. In an attempt to provide uniformity on the definition, diagnosis and treatment of poor responders, a worldwide survey was conducted asking IVF professionals a set of questions on this complex topic. The survey was posted on www.IVF-worldwide.com, the largest and most comprehensive IVF-focused website for physicians and embryologists. A total of 196 centres replied, forming a panel of IVF units with a median of 400 cycles per year. The present study shows that the definition of poor responders is still subjective, and many practices do not use evidence-based treatment for this category of patients. Our hope is that by leveraging the great potential of the internet, future studies may provide immediate large-scale sampling to standardize both poo...

Topics in Cancer Survivorship, 2012

Clinical Physics and Physiological Measurement, 1989

The fetal electrocardiogram (ECG) was recorded from the maternal abdomen together with sonographi... more The fetal electrocardiogram (ECG) was recorded from the maternal abdomen together with sonographic detection of fetal states in four pregnant patients at 26 and 36 weeks of gestation. Computerised algorithms obtained a good recognition of maternal ECG and fetal ECG. The corresponding power spectral density (PSD) was estimated during epochs of quiet or breathing movements for 256 consecutive heart beats. At 36 weeks of gestation the PSD analysis showed heart rate variability components similar to an adult heart. A low frequency component was observed together with a high frequency component in the range of fetal breathing movements. This high frequency component (0.6 - 0.9 Hz) disappeared from the PSD analysis during epochs of apnea. To our knowledge this is the first demonstration of such a mechanism in the human fetus in utero. At 26 weeks no respiratory component was observed in the PSD analysis. The maturation of control mechanisms could be responsible for this difference.

Human Reproduction, 2002

This paper describes an unusual association of aspermia and untreatable, chronic testicular pain ... more This paper describes an unusual association of aspermia and untreatable, chronic testicular pain in a young man who underwent 14 surgical interventions for an imperforate anus. Physical examination and ultrasonography revealed left epididymal and vas enlargement, normal-sized testes, tubular ectasia of the left rete testis and a small intraprostatic paramedian left cyst. Retrograde ejaculation and urogenital infections were excluded, and the FSH and karyotype results were normal. The patient gave his consent to an exploratory intervention with possible radical left orchiectomy. The patency of the left distal seminal duct was unexpectedly normal, and no sperm were found in the epididymis or vas deferens despite their obstructive appearance. Sperm were only found in a 'testicular touch' preparation. The removed testis was immediately opened and most of the testicular lobules were removed, thus allowing the extraction of 25⍥10 6 sperm, which were cryopreserved in 35 straws. An 8-month follow-up examination documented the complete absence of pain and, during the next few months, it is planned to use the thawed sperm for ICSI. Radical orchiectomy plus the cryopreservation of sperm extracted from the whole testis must be considered in the case of the coexistence of chronic unilateral testicular pain and aspermia.

Fertility and Sterility, 2002

Fertility and Sterility, 2007

laboratory to assess the sperm prior to cycle initiation, to anticipate the difficult cases and t... more laboratory to assess the sperm prior to cycle initiation, to anticipate the difficult cases and to maximize sample screening time.

This study evaluates if the pandemic has influenced ART outcome in an asymptomatic infertile popu... more This study evaluates if the pandemic has influenced ART outcome in an asymptomatic infertile population treated at one of the major COVID-19 epicenters during the weeks immediately preceding the lockdown. All ART procedures during two time periods were used for comparison: November 1st, 2018 to February 28th, 2019 (non COVID-19 risk) and November 1st, 2019 to February 29th, 2020 (COVID-19 risk). We analyzed 1,749 fresh cycles (883 non COVID-19 risk and 866 COVID- 19 risk), 1,166 embryo and 63 oocytes warming cycles (538 and 37 during non COVID and 628 and 26 during COVID-19 risk respectively). Clinical pregnancies per cycle were not different: 370 (25,38%) in non COVID vs 415 (27,30%) (p=0.237) during COVID-19 risk. There were no differences in biochemical pregnancy rates 52 (3,57%) vs 38 (2,50%) (p=0.089) nor in ectopic pregnancies 4 (1,08%) vs 3 (0,72%) (p=0,594), spontaneous abortions 84 (22,70%) vs 103 (24,82%) p=0,487, intrauterine ongoing pregnancies 282 (76,22%) vs 309 (74,46...

Antioxidants

Basic scientific research on human reproduction and oxidative damage has been extensively perform... more Basic scientific research on human reproduction and oxidative damage has been extensively performed; however, a more clinical view is still lacking. As a result, exhaustive data on the influence of oxidative stress on human ovarian response and, consequently, on fertility are still lacking. This narrative review aims at summarizing the role of oxidative stress in different conditions associated to female infertility and to list some of the main antioxidant agents. A systematic literature search was performed in May 2022 to retrieve studies regarding the oxidative stress and the human ovarian response from somatic ovarian cells to oocytes damage. Only human studies were included and the authors focused their review, in particular, on clinical implications in order to define a new research perspective on the assessment of any eventual strategy to preserve women’s fertility. Thereby, the authors evaluated the contribution of DNA repair pathways in improving women’s fertility by reducin...

Antioxidants, 2021

The reduction of female fertility over time is considered as a natural consequence of ovarian agi... more The reduction of female fertility over time is considered as a natural consequence of ovarian aging. The exact mechanism underlying this process is not fully elucidated. However, it is becoming increasingly evident that qualitative and quantitative mitochondrial genome alterations might play a relevant role. The former include mitochondrial DNA (mtDNA) damage caused by oxidative stress, the accumulation of acquired mtDNA mutations, the effects of inherited mtDNA mutations, and alterations in the mitochondrial stress response mechanism. The latter refer to alterations in the oocytes, granuolosa cells, and embryonic cells mtDNA content. The present review aims to investigate the evidence about: (1) the effect of qualitative and quantitative mtDNA alterations on female fertility, paying particular attention to those with a pathophysiology characterized by a relevant role of oxidative stress; (2) the use of oocytes, granulosa cells (GCs), embryonic cells, and peripheral blood cells mtDN...

Reproductive BioMedicine Online, 2020

The COVID-19 pandemic is an unprecedented global situation. As assisted reproductive technology (... more The COVID-19 pandemic is an unprecedented global situation. As assisted reproductive technology (ART) specialists, we should be cautious, carefully monitoring the situation while contributing by sharing novel evidence to counsel our patients, both pregnant women and would-be mothers. Time to egg collection and drop-out rates are critical parameters for scheduling treatments once the curve of infections has peaked and plateaued in each country. In order to reduce the values for these two parameters, infertile patients now require even more support from their IVF team: urgent oocyte collection for oncology patients must be guaranteed, and oocyte retrievals for women of advanced maternal age and/or reduced ovarian reserve cannot be postponed indefinitely. This document represents the position of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) in outlining ART priorities during and after this emergency.

Fertility and Sterility, 2018

The simplified SART embryo scoring system is highly correlated to implantation and live birth in ... more The simplified SART embryo scoring system is highly correlated to implantation and live birth in single blastocyst transfers. Journal of assisted reproduction and genetics, 30(4), 563-567.

Frontiers in Endocrinology, 2019

The aim of the present study is to report our experience on elective women fertility preservation... more The aim of the present study is to report our experience on elective women fertility preservation before cancer treatment. Study Design: This is a single-center retrospective observational study, including all patients who underwent elective fertility preservation before oncological treatment between January 2001 and March 2019 at our Institute. Results: Of a total of 568 women who received fertility counseling, 244 (42.9%) underwent 252 oocyte retrieval cycles after controlled ovarian stimulation for cryopreservation. The majority of patients were diagnosed with breast cancer (59.9%), followed by women affected by Hodgkin's and non-Hodgkin's lymphoma (27.4%). A minority comprised patients diagnosed with other malignancies that affected soft tissues (2.8%), ovary borderline type (2.4%), digestive system (1.6%), leukemia (1.6%), uterine cervix (1.2%). The remaining 3.1% were affected by other cancer types. The mean age of the cohort was 31.3 ± 6.4 years and the mean oocyte retrieval was 13.5± 8.4. Of 11 women who returned to attempt a pregnancy, three performed two thawed cycles. We obtained four pregnancies from 24 embryo transfers (Pregnancy Rate 36.4% for couple): two miscarriages and two live births. Overall, 95.7% of oocytes are still in storage. Conclusions: A close collaboration between Cancer and Fertility Center in a tertiary care hospital is essential to provide a good health service in oncological patients. Offering fertility preservation is no longer considered optional and must be included in every therapeutic program for women who receive an oncological diagnosis in their reproductive age. Oocyte cryopreservation appears to be a good opportunity for fertility preservation. Our results, although they are obtained in a small sample, are encouraging, even if only 4.5% of patients returned to use their gametes.

Human Reproduction, 2018

Can a second round of biopsy, vitrification and chromosomal testing provide a valid diagnosis whe... more Can a second round of biopsy, vitrification and chromosomal testing provide a valid diagnosis where the first attempt fails? SUMMARY ANSWER: The risk of inconclusive chromosomal-assessment after trophectoderm biopsy was 2.5% but a further biopsy and vitrification-warming appeared not to impair the competence of euploid blastocysts. WHAT IS KNOWN ALREADY: The increasing implementation of multicell trophectoderm biopsy has significantly reduced the risk of inconclusive diagnosis after preimplantation-genetic-testing (PGT). Yet, few reports have defined the variables that influence the risk of failure or described the technical and clinical outcomes after re-biopsy. STUDY DESIGN, SIZE, DURATION: Retrospective multicenter study involving 8990 blastocyst biopsies conducted between April 2013 and September 2017 at six IVF centers but analyzed at a single genetic laboratory. A total of 206 blastocysts were successfully re-biopsied after warming and re-expansion, then re-vitrified. And 49 of these blastocysts were diagnosed euploid and used in single-embryo-transfers (SETs). Logistic regression analyses were conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 3244 PGT-for-aneuploidies (PGT-A) cycles with a freeze-all approach, vitrification and qPCR-based analysis were performed by 2687 consenting couples. DNA amplification failure (AF) or nonconcurrent data resulted in inconclusive diagnoses. In case of DNA amplification, the cellularity of the biopsy was estimated according to a previously validated method. Euploid SETs were performed. Clinical pregnancy, miscarriage, live birth rates (LBR) and perinatal outcomes were monitored. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 2.5% of trophectoderm biopsies resulted in an inconclusive diagnosis (N = 228/8990). Specifically, 2% (N = 176/8990) resulted in AF and 0.5% (N = 52/8990) in non-concurrent results. The only parameters significantly associated with inconclusive diagnoses were the IVF center and the embryo age (days) at biopsy. Among samples with successful amplification, the number of cells in the biopsy and the day of biopsy were critical to limit non-concurrent results. In total, 213 blastocysts with an

Frontiers in Endocrinology, 2019

To study the actual controlled ovarian stimulation (COS) management in women with suboptimal resp... more To study the actual controlled ovarian stimulation (COS) management in women with suboptimal response, comparing clinical outcomes to the gonadotropins consume, considering potential role of luteinizing hormone (LH) addition to follicle-stimulating hormone (FSH). Design: Monocentric, observational, retrospective, real-world, clinical trial on fresh intra-cytoplasmic sperm injection (ICSI) cycles retrieving from 1 to 9 oocytes, performed at Humanitas Fertility Center from January 1st, 2012 to December 31st, 2015. Methods: COS protocols provided gonadotropin releasing-hormone (GnRH) agonist long, flare-up, short and antagonist. Both recombinant and urinary FSH were used for COS and LH was added according to the clinical practice. ICSI outcomes considered were: gonadotropins dosages; total, mature, injected and frozen oocytes; cumulative, transferred and frozen embryos; implantation rate; pregnancy, delivery and miscarriage rates. Outcomes were compared according to the gonadotropin regimen used during COS. Results: Our cohort showed 20.8% of low responders, defined as 1-3 oocytes retrieved and 79.2% of "suboptimal" responders, defined as 4-9 oocytes retrieved. According to recent POSEIDON stratification, cycles were divided in group 1 (6.9%), 2 (19.8%), 3 (11.7%), and 4 (61.5%). The cohort was divided in 3 groups, according to the gonadotropin's regimen. Women treated with FSH plus LH showed worst prognostic factors, in terms of age, basal FSH, AMH, and AFC. This difference was evident in suboptimal responders, whereas only AMH and AFC were different among treatment groups in low responders. Although a different result, in terms of oocytes and embryos detected, major ICSI outcomes (i.e., pregnancy and delivery rates) were similar among groups of COS treatment. Outcomes were significantly different among Poseidon groups. Implantation, pregnancy and delivery rates were significantly higher in Poseidon group 1 Levi-Setti et al. Low Prognosis Women in IVF and progressively declined in other POSEIDON groups, reaching the worst percentage in group 4. Conclusions: In clinical practice, women with worst prognosis factors are generally treated with a combination of LH and FSH. Despite low prognosis women showed a reduced number of oocytes retrieved, the final ICSI outcome, in terms of pregnancy, is similarly among treatment group. This result suggests that the LH addition to FSH during COS could improve the quality of oocytes retrieved, balancing those differences that are evident at baseline.

Journal of Assisted Reproduction and Genetics, 2018

Archivio Italiano di Urologia e Andrologia, 2017

Background: antioxidants supplementation improves sperm quality, but few trials have analyzed the... more Background: antioxidants supplementation improves sperm quality, but few trials have analyzed the effects on sperm DNA fragmentation (SDF). This study compares the effectiveness of SOD-based antioxidant supplementation plus hydroxytyrosol and carnosol in reducing SDF with other antioxidants without SOD, hydroxytyrosol, and carnosol. Materials and methods: men with high SDF at baseline were selected in our clinical database. The patients taken into account had a 2-month control. SDF was measured by Sperm Chromatin Dispersion test (SCD). Untreated men were used as a control group. The remaining subjects received some oral antioxidant supplements (12 different combinations of both hydrophilic and lipophilic antioxidants), with some of them receiving nutritional support with a SOD-based antioxidant supplementation plus hydroxytyrosol and carnosol. Results: 118 men were selected for a retrospective study. Mean age 39.3 ± 5.4 years. Fifteen had no treatment, 55 were treated with a SOD-bas...

Journal of assisted reproduction and genetics, Jan 6, 2016

The etiology of maternal aging, a common cause of female factor infertility and a rate-limiting s... more The etiology of maternal aging, a common cause of female factor infertility and a rate-limiting step in vitro fertilization (IVF) success, remains still unclear. Proteomic changes responsible for the impaired successful pregnancy outcome after IVF with aged blastocysts have not been yet evaluated. The objective of this prospective study was to employ proteomic techniques and bioinformatic tools to enlight differences at the protein level in blastocoel fluid of aged and younger woman. Protein composition of human blastocoel fluid isolated by micromanipulation from 46 blastocysts of women aged <37 years (group A) and 29 of women aged ≥37 years (group B) have been identified by a shotgun proteomic approach based on high-resolution nano-liquid chromatography electrospray-ionization-tandem mass spectrometry (nLC-ESI-MS/MS) using label free for the relative quantification of their expression levels. The proteomic analysis leads to the identification and quantification of 148 proteins; ...

Journal of Assisted Reproduction and Genetics, 2016

The aim of this study was to provide a comprehensive follow-up of fetal and perinatal outcome and... more The aim of this study was to provide a comprehensive follow-up of fetal and perinatal outcome and the incidence of congenital anomalies in babies born after fresh embryo transfers compared to those conceived spontaneously in infertile couples. Methods Retrospective comparative analysis of all clinical pregnancies from fresh cleavage-stage embryo transfer cycles (IVF and ICSI) compared with infertile patients who conceived spontaneously in the same time period (control). Congenital anomalies were classified following the European Surveillance of Congenital Anomalies (EUROCAT) classification. Results A total of 2414 assisted reproductive technology (ART) pregnancies were compared to 582 spontaneous conceptions in the control infertile group representing 2306 deliveries. No significant differences were found in pregnancy outcome between the two groups (delivery rate, abortion rate, ectopic pregnancies, medical abortions for fetal anomalies, single and twins mean gestational age, and weight at delivery). A significant difference (p < 0.001) was found in the twin (21.3 vs 2.3 %) and triplet rates (2.3 vs 0 %). A total of 2351 babies were delivered in the ART group and 449 in the control group. A total of 90 babies (3.8 %) were diagnosed with a major congenital anomaly in the ART group and 15 (3.3 %) in the control group (p = ns). The overall rate of major congenital anomalies (105/2800) in ART and spontaneous pregnancies in infertile couples was significantly higher when compared to the EUROCAT 2.0 versus 3.75 % (p = 0.0002). Discussion Babies born after ART treatments and from spontaneous conception in infertile couples had rates of congenital anomalies higher than those recorded by the EUROCAT. However, the rates of anomalies were not different within the infertile population whether conceived by ART or spontaneously. These data suggest that the diagnosis of infertility in itself is the common denominator for the increase in the rates of anomalies seen in both ART and spontaneous conceptions.

Reproductive BioMedicine Online, 2016

In addition, he received a PhD degree in neuroscience physiology and biomedical engineering from ... more In addition, he received a PhD degree in neuroscience physiology and biomedical engineering from the University of Bologna and the University of California at Berkley. His post doctorate was done at the Center for Biostabilization at the University of California at Davis. He has published over 150 scientific papers in peer-reviewed journals and filed over 60 patents and is the recipient of many prizes for basic and applied research.

Journal of Fertilization: In vitro, 2012

In March 2004 the Italian Parliament enacted a Law (Law 40/2004) establishing a long list of rest... more In March 2004 the Italian Parliament enacted a Law (Law 40/2004) establishing a long list of restrictions for ART procedures. The law articles were constructed around the assumption of considering the embryo as a human being, with the same or even more rights of the woman or the couple seeking treatment for their infertility-related childless. In detail, the Law obliged to use only 3 oocytes to be fertilised and all the resulting embryos had to be transferred. Embryo freezing as well as pre implantation screening (PGS) or diagnosis (PGD) and sperm or oocytes donation were forbidden. In May 2009 the Italian Constitutional Court was called to judge parts of the Law 40 and cancelled some of the restrictions since they violated women's rights to have access to the best possible treatment with the lower health risks for both her and the future children. The Constitutional Court stated that the decision on the number of oocytes to be used for insemination, the embryos to be transferred and the embryos to be frozen were a matter of good clinical practice and under the full responsibility of the reproductive specialist. PGD and PGS remains a matter of debate because the Court was not called specifically to address this subject, although a clear opinion in favour has been expressed in previous decisions. The Constitutional Court will be called only in the future to express a judgement on gametes donation that is still forbidden. The present work reviews the clinical and social effects produced by 5 years of a restrictive ART Law (2004-2009); the preliminary results after the Italian Constitutional Court decision (May-December 2009 and comments on cross border infertility treatment for procedures that are still barred.

Reproductive biomedicine online, Jan 16, 2015

Poor responders represent a significant percentage of couples treated in IVF units (10-24%), but ... more Poor responders represent a significant percentage of couples treated in IVF units (10-24%), but the standard definition of poor responders remains uncertain and consequently optimal treatment options remain subjective and not evidence-based. In an attempt to provide uniformity on the definition, diagnosis and treatment of poor responders, a worldwide survey was conducted asking IVF professionals a set of questions on this complex topic. The survey was posted on www.IVF-worldwide.com, the largest and most comprehensive IVF-focused website for physicians and embryologists. A total of 196 centres replied, forming a panel of IVF units with a median of 400 cycles per year. The present study shows that the definition of poor responders is still subjective, and many practices do not use evidence-based treatment for this category of patients. Our hope is that by leveraging the great potential of the internet, future studies may provide immediate large-scale sampling to standardize both poo...

Topics in Cancer Survivorship, 2012

Clinical Physics and Physiological Measurement, 1989

The fetal electrocardiogram (ECG) was recorded from the maternal abdomen together with sonographi... more The fetal electrocardiogram (ECG) was recorded from the maternal abdomen together with sonographic detection of fetal states in four pregnant patients at 26 and 36 weeks of gestation. Computerised algorithms obtained a good recognition of maternal ECG and fetal ECG. The corresponding power spectral density (PSD) was estimated during epochs of quiet or breathing movements for 256 consecutive heart beats. At 36 weeks of gestation the PSD analysis showed heart rate variability components similar to an adult heart. A low frequency component was observed together with a high frequency component in the range of fetal breathing movements. This high frequency component (0.6 - 0.9 Hz) disappeared from the PSD analysis during epochs of apnea. To our knowledge this is the first demonstration of such a mechanism in the human fetus in utero. At 26 weeks no respiratory component was observed in the PSD analysis. The maturation of control mechanisms could be responsible for this difference.

Human Reproduction, 2002

This paper describes an unusual association of aspermia and untreatable, chronic testicular pain ... more This paper describes an unusual association of aspermia and untreatable, chronic testicular pain in a young man who underwent 14 surgical interventions for an imperforate anus. Physical examination and ultrasonography revealed left epididymal and vas enlargement, normal-sized testes, tubular ectasia of the left rete testis and a small intraprostatic paramedian left cyst. Retrograde ejaculation and urogenital infections were excluded, and the FSH and karyotype results were normal. The patient gave his consent to an exploratory intervention with possible radical left orchiectomy. The patency of the left distal seminal duct was unexpectedly normal, and no sperm were found in the epididymis or vas deferens despite their obstructive appearance. Sperm were only found in a 'testicular touch' preparation. The removed testis was immediately opened and most of the testicular lobules were removed, thus allowing the extraction of 25⍥10 6 sperm, which were cryopreserved in 35 straws. An 8-month follow-up examination documented the complete absence of pain and, during the next few months, it is planned to use the thawed sperm for ICSI. Radical orchiectomy plus the cryopreservation of sperm extracted from the whole testis must be considered in the case of the coexistence of chronic unilateral testicular pain and aspermia.

Fertility and Sterility, 2002

Fertility and Sterility, 2007

laboratory to assess the sperm prior to cycle initiation, to anticipate the difficult cases and t... more laboratory to assess the sperm prior to cycle initiation, to anticipate the difficult cases and to maximize sample screening time.