Massimo Candiani - Academia.edu (original) (raw)

Papers by Massimo Candiani

Research paper thumbnail of Evaluation of Uterine Artery Doppler and Estrogen Milieu in Oocyte Donation Pregnancies—A Pilot Study

Diagnostics

Oocyte donations (OD) represent 4.5% of all in vitro fertilization (IVF) cycles. While OD pregnan... more Oocyte donations (OD) represent 4.5% of all in vitro fertilization (IVF) cycles. While OD pregnancies face increased risks of obstetrical complications, especially pregnancy-induced hypertension and pre-eclampsia (PE), little is known about the physiology and the physiopathology of placentation. We performed a prospective case-control study to analyze uterine artery Doppler pulsatility index (UtA-PI) and serum maternal 17β-estradiol (17β-E) at 11 + 0 to 13 + 6 weeks’ gestation in singleton pregnancies with different modes of conception. Study groups were: 55 OD, 48 IVF with autologous oocytes from fresh cycles (Autologous-Fresh IVF), 10 IVF with autologous oocytes from frozen cycles (Autologous-Frozen IVF) and 122 spontaneously conceived pregnancies (SC). The mean UtA-PI and serum maternal 17β-E at 11 to 13 + 6 weeks were significantly lower in OD as compared to SC and autologous IVF, either from fresh or frozen cycles. Oocyte donation presents lower UtA-PI and lower serum 17β-E in ...

Research paper thumbnail of Fertility sparing surgery in epithelial ovarian cancer in Italy: perceptions, practice, and main issues

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 2018

About 2.7% of patients epithelial ovarian cancers (EOC) are younger than 40 and present with stag... more About 2.7% of patients epithelial ovarian cancers (EOC) are younger than 40 and present with stage I disease. For this subset of women, the issue of fertility sparing surgery (FSS) has become critical. The aim of this survey was to investigate the management of EOC patients desiring to preserve fertility in Italy. A questionnaire consisting of 30 items was developed to evaluate: patient-selection criteria, rate of FSS, patient's counseling- and pregnancy-timing, fertility preservation, obstetrics, and oncologic outcomes. One expert clinician for each of 50 major gynecologic oncology centers was invited to participate. Data were entered into a database and statistically analyzed. 74% of questionnaires were complete. The proportion of EOC patients treated with FSS was <10%, 10%-20% and >20% in 70.3%, 24.3% and 5.4% of cases, respectively. Age, fertility preservation desire, histotype, and stage were considered relevant to select patients for a conservative treatment for 64.8...

Research paper thumbnail of Neoadjuvant chemotherapy in high-risk ovarian cancer patients: Role of age

Tumori, Jan 29, 2018

To review a single-center clinical experience with neoadjuvant chemotherapy (NACT) in a populatio... more To review a single-center clinical experience with neoadjuvant chemotherapy (NACT) in a population of frail epithelial ovarian cancer (EOC) patients and investigate the prognostic role of advanced age. We retrospectively reviewed clinical data from 102 advanced EOC patients treated with NACT and presenting high perioperative risk. Patients were divided into 2 groups: group A, including patients aged 70 years or older; and group B, including patients below 70 years old. Univariate and multivariate analyses were performed to compare survival and prognostic factors for survival between the two groups. Forty-two patients (41.2%) were older than 70 years. Elderly patients were more likely to present comorbidities ( p = .0001), poor performance status ( p = .04), and multiple indications for NACT ( p = .03). They showed a reduced response to NACT, since only 64% of elderly patients underwent surgical debulking (98.3% vs 64.3%, p = .001) and, among these, half of them were optimally debulk...

Research paper thumbnail of {"__content__"=>"Early Regenerative Modifications of Human Postmenopausal Atrophic Vaginal Mucosa Following Fractional CO Laser Treatment.", "sub"=>{"__content__"=>"2"}}

Open access Macedonian journal of medical sciences, Jan 25, 2018

Postmenopausal women experience undesired symptoms that adversely affect their quality of life. I... more Postmenopausal women experience undesired symptoms that adversely affect their quality of life. In the recent years, a specific 12 - week fractional CO laser treatment has been introduced, with highly significant relief of symptoms. The aim of this paper is the identification of the early modifications of structural components of atrophic vaginal mucosa induced by laser irradiation, which is responsible for the restorative processes. We investigated by microscopical, ultrastructural and biochemical methods the modifications of the structural components of postmenopausal atrophic vaginal mucosa tissues after 1 hour following a single fractional laser CO application. In one hour, the mucosal epithelium thickens, with the maturation of epithelial cells and desquamation at the epithelial surface. In the connective tissue, new papillae indenting the epithelium with newly formed vessels penetrating them, new thin fibrils of collagen III are also formed in a renewed turnover of components ...

Research paper thumbnail of Fertility preservation in women harboring deleterious BRCA mutations: ready for prime time?

Human reproduction (Oxford, England), 2017

Fertility issues have become critical in the management and counseling of BRCA mutation carriers.... more Fertility issues have become critical in the management and counseling of BRCA mutation carriers. In this setting four points deserve consideration. (1) Women in general lose their ability to conceive at a mean age of 41 years, thus the suggested policy of prophylactic bilateral salpingo-oophorectomy at age 40 for BRCA mutation carriers does not affect the chances of natural pregnancy. Conversely, if the procedure is chosen at 35 years old, oocyte cryopreservation prior to surgery should be considered. (2) Some evidence suggests that ovarian reserve may actually be partly reduced in BRCA mutations carriers and that the mutation may affect ovarian responsiveness to stimulation. However, these findings are still controversial. (3) Breast cancer is not rare before the age of 40 and fertility preservation after diagnosis can be requested in a significant proportion of BRCA mutation carriers. Thus, a policy of oocyte cryopreservation in young healthy carriers deserves consideration. The ...

Research paper thumbnail of Comparison of Laparoscopy and Laparotomy Staging of Early-Stage Ovarian Cancer: A Study with 12-Year Experience

Journal of Minimally Invasive Gynecology

Research paper thumbnail of Sexual Function in Women Suffering From Genitourinary Syndrome of Menopause Treated With Fractionated CO2 Laser

Sexual medicine reviews, Jan 23, 2017

Genitourinary syndrome of menopause (GSM) has a significant impact on the trophism of the genital... more Genitourinary syndrome of menopause (GSM) has a significant impact on the trophism of the genital and lower urinary tracts and can considerably impair sexual function. Fractional CO2 laser has a regenerative effect on vulvovaginal tissue trophism after menopause. To review the available literature on the effect of fractional CO2 laser on the sexual function of postmenopausal women affected by GSM. A database search was carried out using the terms CO2laser, vaginal atrophy, sexual function, dyspareunia, and genitourinary syndrome of menopause and excluding studies using other types of laser or including breast cancer survivors with vulvovaginal atrophy. For statistical analysis, the estimated overall laser effect was computed (when at least two studies were involved) and data type of generic inverse variance was computed using inverse variance as the statistical method, a random-effects model, and the difference in means as an effect measurement. Different methods of evaluating sexua...

Research paper thumbnail of Advances in improving fertility in women through stem cell-based clinical platforms

Expert opinion on biological therapy, 2017

Due to their regenerative ability, stem cells are looked at as a promising tool for improving inf... more Due to their regenerative ability, stem cells are looked at as a promising tool for improving infertility treatments in women. As the main limiting factor in female fertility is represented by the decrease of ovarian reserve, the main goals of stem cell-based clinical platforms would be to obtain in vitro or in vivo neo-oogenesis. Refractory endometrial factor infertility also represents an obstacle for female reproduction for which stem cells might provide novel treatment strategies. Areas covered: A systematic search of the literature was performed on MEDLINE/PubMed database to identify relevant articles using stem-cell based clinical or research platforms in the field of female infertility. Expert opinion: In vitro oogenesis has not so far developed beyond the stage of oocyte-like cells whose normal progression to mature oocytes and ability to be fertilized was not proved. Extensive epigenetic programming of gamete precursors and the complex interactions between somatic and germ ...

Research paper thumbnail of Long-acting recombinant FSH in random start ovarian stimulation protocols for fertility preservation in women with cancer

Acta obstetricia et gynecologica Scandinavica, Jan 6, 2017

The objective of this study was to assess effectiveness and the potential benefits of the use of ... more The objective of this study was to assess effectiveness and the potential benefits of the use of long-acting recombinant follicle-stimulating hormone (FSH) in random-start protocol for fertility preservation in women with cancer. This is a retrospective before and after study performed between February 2013 and December 2015 in women that underwent ovarian hyper-stimulation for oocyte cryobanking using a random start approach. In the first part of the study period, the subjects were treated with daily recombinant FSH whereas in the second part the stimulation was initiated with long-acting recombinant FSH. The primary aim of the study was to compare the number of oocytes stored in the two study periods. 140 women were ultimately selected. Compared to daily recombinant FSH, the use of the long-acting compound was associated with a reduced number of injections (12.5 ± 3.5 vs 16.4 ± 0.3; p<0.001) and a longer duration of stimulation (11.4 ± 1.9 vs 10.6 ± 1.9, p=0.01). Conversely, th...

Research paper thumbnail of Nuchal translucency measurement, free β-hCG and PAPP-A concentrations in IVF/ICSI pregnancies: systematic review and meta-analysis

Prenatal diagnosis, Jan 17, 2017

So far data on the effect of assisted reproductive technologies (ART) on the components of first ... more So far data on the effect of assisted reproductive technologies (ART) on the components of first trimester combined screening for Down syndrome are still controversial. A systematic search of the literature was performed in order to identify the effect of ART, particularly IVF and ICSI with fresh embryo transfer, on the nuchal translucency (NT), free β-hCG and PAPP-A measurements. Moreover, a meta-analysis and a descriptive graphical representation of the ratios between ART and spontaneous pregnancies (controls) values of median of the multiple of median (m0MOM) was performed. Free β-hCG test showed slightly higher values in the ICSI group than controls (RR = 1.09, 95%CI: 1.03-1.16) but not in the IVF group (RR = 1.03, 95%CI: 0.94-1.12). PAPP-A values for IVF/ICSI, IVF and ICSI showed lower values in comparison with controls (RR, 95%CI 0.85, 0.80-0.90; 0.82, 0.74-0.89 and 0.83, 0.79-0.86 respectively). The NT measurement did not show any statistical differences between study groups ...

Research paper thumbnail of Bladder Endometriosis: A Systematic Review of Pathogenesis, Diagnosis, Treatment, Impact on Fertility, and Risk of Malignant Transformation

European urology, Jan 28, 2016

The bladder is the most common site affected in urinary tract endometriosis. There is controversy... more The bladder is the most common site affected in urinary tract endometriosis. There is controversy regarding the pathogenesis, clinical management (diagnosis and treatment), impact on fertility, and risk of malignant transformation of bladder endometriosis (BE). To systematically evaluate evidence regarding the pathogenesis, diagnosis, medical and surgical treatment, impact on female fertility, and risk of malignant transformation of BE. A systematic review of PubMed/Medline from inception until October 2016 was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and was registered in the PROSPERO registry (www.crd.york.ac.uk/prospero; CRD42016039281). Eighty-seven articles were selected for inclusion in this analysis. BE is defined as the presence of endometrial glands and stroma in the detrusor muscle. Ultrasonography is the first-line technique for assessment of BE owing to its accuracy, safety, and cost. Clinical m...

Research paper thumbnail of Thoracic Endometriosis Syndrome: Association With Pelvic Endometriosis and Fertility Status

Journal of Minimally Invasive Gynecology, 2017

To evaluate associations among catamenial pneumothorax, pelvic endometriosis, and fertility statu... more To evaluate associations among catamenial pneumothorax, pelvic endometriosis, and fertility status. Retrospective study (Canadian Task Force classification II-2). Departments of Thoracic Surgery and Obstetrics and Gynecology, San Raffaele Hospital, Milan, Italy. Sixteen females referred to the Department of Thoracic Surgery for treatment of spontaneous pneumothorax between January 2001 and January 2014 and referred to the outpatient clinic for gynecologic follow-up. Thoracoscopy for catamenial pneumothorax and laparoscopy for pelvic endometriosis. Characteristics of the patients, the presence of endometriosis, and their fertility status were statistically analyzed. Pelvic endometriosis was diagnosed in 9 patients (56.3%), but 6 patients did not undergo a laparoscopic procedure to confirm or exclude the disease. Seven of the affected patients (77.8%) had stage III-IV endometriosis. Two-thirds of the patients with pelvic endometriosis who attempted conception conceived spontaneously, as did all of the patients without histopathological confirmation of endometriosis. Thoracic endometriosis syndrome, characterized mainly by catamenial pneumothorax, is a relevant condition in patients affected by endometriosis. However, few previous studies have analyzed this condition from a gynecologic standpoint, in terms of characteristics of endometriosis and fertility status of affected women. Our findings support the presence of a strong association between catamenial pneumothorax and pelvic endometriosis, as well as a minimal effect of catamenial pneumothorax on fertility status, even in the presence of pelvic endometriosis.

Research paper thumbnail of Pregnancy outcome in women with endometriosis achieving pregnancy with IVF

Human Reproduction, 2016

Women with endometriosis who conceive with IVF do not face an increased risk of preterm birth. WH... more Women with endometriosis who conceive with IVF do not face an increased risk of preterm birth. WHAT IS KNOWN ALREADY: The eutopic endometrium of women with endometriosis has been repeatedly shown to present molecular and cellular alterations. On this basis, it has been hypothesized that pregnancy outcome may be altered in affected women. However, to date, available evidence from epidemiological studies is scanty and conflicting. Data tended to be partly consistent only for an increased risk of preterm birth and placenta previa. STUDY DESIGN, SIZE, DURATION: Retrospective matched case-control study of women achieving an IVF singleton pregnancy progressing beyond 12 weeks' gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women achieving IVF singleton pregnancies that progressed beyond 12 weeks' gestation at two infertility units were reviewed. Cases were women with a history of surgery for endometriosis and/or with a sonographic diagnosis of the disease at the time of the IVF cycle. Controls were women without current or past evidence of endometriosis who were matched to cases by age (± 6 months), type of cycle (fresh or frozen cycle) and study period. Male factor and unexplained infertility were the most common diagnoses in the control group. Two hundred and thirty-nine women with endometriosis and 239 controls were selected. The main outcome of the study was the rate of preterm birth (birth < 37 weeks' gestation) regardless of the cause. Secondary analyses were performed for the most common obstetrical complications. MAIN RESULTS AND THE ROLE OF CHANCE: The rate of preterm birth was similar in the two study groups (14% and 14%, respectively, p = 0.89). The rate of live birth and the incidence of hypertensive disorders, gestational diabetes, small and large for gestational age newborns and neonatal problems also did not differ. In contrast, placenta previa was more common in women with endometriosis than controls (6% versus 1%, respectively; p = 0.006): The adjusted odds ratio was 4.8 (95% confidence interval: 1.4-17.2). LIMITATIONS, REASONS FOR CAUTION: As for all observational studies, confounders cannot be totally excluded. Moreover, the retrospective study design exposes the findings to some inaccuracies. For example, the independent role of adenomyosis could not be reliably assessed because this diagnosis is complex and would necessitate a prospective recruitment. Second, the selection of controls may also be a matter of concern because some affected women may have been erroneously included in this group. Third, even if the sample size is significant, it is insufficient for robust subgroup analyses. Finally, it is mandatory to point out that our conclusions are valid for IVF pregnancies only, and specific data from properly designed studies are required to support any inference for natural pregnancies.

Research paper thumbnail of Fertility preservation in women with borderline ovarian tumours

Cancer Treatment Reviews, 2016

Borderline ovarian tumours (BOT) may occur in young women and have an excellent survival rate. Th... more Borderline ovarian tumours (BOT) may occur in young women and have an excellent survival rate. Therefore, there is the obligation to put emphasis on fertility preservation in affected women. On the other hand, it has also been underlined that the disease should be managed with caution because these tumours can relapse and, albeit rare, malignant transformation can also occur. Unfortunately, evidence on fertility preservation in women with BOT is scanty. In this opinion paper, we tried to draw some clinical indications based on the few available studies on the clinical management of BOT and their possible relation with controlled ovarian hyper-stimulation (COH). We ultimately came to the following conclusions: (1) Fertility counselling should become an integral part of the clinical management of women with BOT. Conservative management without pre-surgical counselling may expose women without reasonable chances of future conceptions to undue risks. (2) Despite some epidemiological concerns on the possible relation between COH and BOT, the conservative surgical treatment should be associated to oocyte cryopreservation considering the high risk of recurrence of the disease. (3) Letrozole during COH should be considered to temper the theoretical risk of increased recurrences. (4) Pregnancy should not be delayed in women at low-moderate risk of recurrences. Fertility preservation may be avoided in these women provided that they start active pregnancy seeking early. (5) Albeit experimental, oocytes retrieval from affected ovaries removed at the time of surgery can be considered. Conversely, ovarian cortex cryopreservation is not justified given the possible risks of malignant reseeding.

Research paper thumbnail of Application of failure mode and effect analysis in an assisted reproduction technology laboratory

Reproductive biomedicine online, Jan 24, 2016

Assisted reproduction technology laboratories have a very high degree of complexity. Mismatches o... more Assisted reproduction technology laboratories have a very high degree of complexity. Mismatches of gametes or embryos can occur, with catastrophic consequences for patients. To minimize the risk of error, a multi-institutional working group applied failure mode and effects analysis (FMEA) to each critical activity/step as a method of risk assessment. This analysis led to the identification of the potential failure modes, together with their causes and effects, using the risk priority number (RPN) scoring system. In total, 11 individual steps and 68 different potential failure modes were identified. The highest ranked failure modes, with an RPN score of 25, encompassed 17 failures and pertained to "patient mismatch" and "biological sample mismatch". The maximum reduction in risk, with RPN reduced from 25 to 5, was mostly related to the introduction of witnessing. The critical failure modes in sample processing were improved by 50% in the RPN by focusing on staff t...

Research paper thumbnail of Creation of a neovagina in Rokitansky patients with a pelvic kidney: comparison of long-term results of the modified Vecchietti and McIndoe techniques

Fertility and Sterility, Mar 1, 2010

To evaluate perioperative data and long-term results of Rokitansky patients with a pelvic kidney ... more To evaluate perioperative data and long-term results of Rokitansky patients with a pelvic kidney that underwent the McIndoe and modified Vecchietti procedures. Design: Retrospective descriptive study. Setting: A tertiary referral center for the study and treatment of Rokitansky syndrome. Patient(s): Eleven patients with Rokitansky syndrome. Intervention(s): Two and nine patients, respectively, underwent the McIndoe and Vecchietti modified techniques. Main Outcome Measure(s): Anatomic success was defined as a neovagina R6 cm long allowing easy introduction of two fingers within 6 months postoperatively. Functional success was considered achieved when the patient reported satisfactory sexual intercourse starting from 6 months postoperatively. Result(s): Surgery was performed with no complications in all 11 patients. The mean duration of surgery was 190 AE 14.1 minutes in the first group and 32 AE 6.4 minutes in the second group. At 14 years of follow-up, both patients who underwent McIndoe vaginoplasty had a mean AE SD length and width of 8.2 AE 0.4 cm and 5 cm and negative Schiller's test 24 months postoperatively. At 4 years of follow-up, eight out of the nine patients who underwent the Vecchietti procedure (89%) had a mean AE SD length and width of the neovagina of 7.4 AE 0.6 cm and 4.2 AE 0.5 cm and iodine-positive vaginal-type epithelium coating 100% of the neovagina 24 months postoperatively. Conclusion(s): While appearing to be safe, effective, and with optimal functional results, the modified Vecchietti approach also seems to yield good anatomical and aesthetic results along with shorter surgical and hospitalization times. (Fertil Steril Ò 2010;93:1280-5. Ó2010 by American Society for Reproductive Medicine.

Research paper thumbnail of Use of knockout transgenic mice in the study of endometriosis : insights from mice lacking β2-microglobulin and interleukin-12p40

Fertility and Sterility, 2001

To test the possibility of using transgenic knockout mice in the study of endometriosis and to in... more To test the possibility of using transgenic knockout mice in the study of endometriosis and to investigate specific immunologic aspects of the disease. Experimental blinded study. Academic research center. Thirty-two mice with experimentally induced endometriosis. Endometriosis was induced in 8 beta(2)-microglobulin-deficient BALB/c mice and 7 wild-type BALB/c controls. Similarly, endometriosis was induced in 8 interleukin-12-deficient C57BL/6 mice and in 9 wild-type C57BL/6 controls. Weight and surface area of endometriotic lesions. Total weight and surface area of endometriotic lesions was markedly lower in beta(2)-microglobulin-deficient BALB/c mice than in wild-type BALB/c controls. A slight but statistically insignificant increase in total weight and surface area of lesions was observed in interleukin-12-deficient C57BL/6 mice compared to wild-type C57BL/6 controls. Knockout transgenic mice can be used successfully for the study of endometriosis; however, in these animals, the redundancy of the immunologic cytokine-mediated regulatory mechanisms may lead to compensation from the remaining genome. Results from beta(2)-microglobulin-deficient mice support the critical role of the immune system in the pathogenesis of the disease.

Research paper thumbnail of Risk of miscarriage in women with endometriosis: insights from in vitro fertilization cycles

Fertility and sterility, Aug 16, 2016

To evaluate whether women with endometriosis achieving singleton pregnancies with IVF face an inc... more To evaluate whether women with endometriosis achieving singleton pregnancies with IVF face an increased risk of miscarriage. Matched case-control study. Infertility units. Women achieving singleton pregnancies with the use of IVF were considered. Cases were women with a history of surgery for endometriosis and those who were documented the presence of ovarian endometriomas at the time of the IVF cycle (n = 313). Controls were matched to cases by age (±6 months), type of cycle (fresh or frozen cycle). and study period (n = 313). Retrospective review of women undergoing IVF. Rate of miscarriage before 12 weeks' gestation. The number of miscarriages in women with and without endometriosis was similar, being 48 (15%) and 60 (19%), respectively. The odds ratio of miscarriage in affected women was 0.76 (95% confidence interval 0.50-1.16). The odds ratio adjusted for body mass index (BMI), parity, duration of infertility, and male factor infertility was 0.81 (95% confidence interval 0....

Research paper thumbnail of Mental Representations of Illness in Patients with Gestational Trophoblastic Disease: How Do Patients Perceive Their Condition?

PloS one, 2016

Gestational Trophoblastic Disease comprises a group of benign and malignant disorders that derive... more Gestational Trophoblastic Disease comprises a group of benign and malignant disorders that derive from the placenta. Using Leventhal's Common-Sense Model as a theoretical framework, this paper examines illness perception in women who have been diagnosed with this disease. Thirty-one women diagnosed with Gestational Trophoblastic Disease in a hospital in Italy were asked to complete the Illness Perception Questionnaire-Revised to measure the following: illness Identity, illness opinions and causes of Gestational Trophoblastic Disease. High mean scores were observed in the Emotional representations and Treatment control subscales. A significant difference emerged between hydatidiform mole patients and those with gestational trophoblastic neoplasia on the Identity subscale. A significant correlation emerged between "time since diagnosis" and the Treatment control subscale. This study is the first to investigate illness perception in Gestational Trophoblastic Disease. From...

Research paper thumbnail of Elevated Systemic Levels of Endocannabinoids and Related Mediators Across the Menstrual Cycle in Women With Endometriosis

Reproductive sciences (Thousand Oaks, Calif.), Aug 17, 2016

Cannabinoids and modulators of the endocannabinoid system affect specific mechanisms that are cri... more Cannabinoids and modulators of the endocannabinoid system affect specific mechanisms that are critical to the establishment and development of endometriosis. The aim of this study was to measure the systemic levels of endocannabinoids and related mediators in women with and without endometriosis and to investigate whether such levels correlated with endometriosis-associated pain. Plasma and endometrial biopsies were obtained from women with a laparoscopic diagnosis of endometriosis (n = 27) and no endometrial pathology (n = 29). Plasma levels of endocannabinoids (N-arachidonoylethanolamine [AEA] and 2-arachidonoylglycerol [2-AG]) and related mediators (N-oleoylethanolamine [OEA] and N-palmitoylethanolamine [PEA]), messenger RNA expression of some of their receptors (cannabinoid receptor type 1 [CB1], CB2, transient receptor potential vanilloid type [TRPV1]), and the enzymes involved in the synthesis (N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D [NAPE-PLD]) and degrada...

Research paper thumbnail of Evaluation of Uterine Artery Doppler and Estrogen Milieu in Oocyte Donation Pregnancies—A Pilot Study

Diagnostics

Oocyte donations (OD) represent 4.5% of all in vitro fertilization (IVF) cycles. While OD pregnan... more Oocyte donations (OD) represent 4.5% of all in vitro fertilization (IVF) cycles. While OD pregnancies face increased risks of obstetrical complications, especially pregnancy-induced hypertension and pre-eclampsia (PE), little is known about the physiology and the physiopathology of placentation. We performed a prospective case-control study to analyze uterine artery Doppler pulsatility index (UtA-PI) and serum maternal 17β-estradiol (17β-E) at 11 + 0 to 13 + 6 weeks’ gestation in singleton pregnancies with different modes of conception. Study groups were: 55 OD, 48 IVF with autologous oocytes from fresh cycles (Autologous-Fresh IVF), 10 IVF with autologous oocytes from frozen cycles (Autologous-Frozen IVF) and 122 spontaneously conceived pregnancies (SC). The mean UtA-PI and serum maternal 17β-E at 11 to 13 + 6 weeks were significantly lower in OD as compared to SC and autologous IVF, either from fresh or frozen cycles. Oocyte donation presents lower UtA-PI and lower serum 17β-E in ...

Research paper thumbnail of Fertility sparing surgery in epithelial ovarian cancer in Italy: perceptions, practice, and main issues

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 2018

About 2.7% of patients epithelial ovarian cancers (EOC) are younger than 40 and present with stag... more About 2.7% of patients epithelial ovarian cancers (EOC) are younger than 40 and present with stage I disease. For this subset of women, the issue of fertility sparing surgery (FSS) has become critical. The aim of this survey was to investigate the management of EOC patients desiring to preserve fertility in Italy. A questionnaire consisting of 30 items was developed to evaluate: patient-selection criteria, rate of FSS, patient's counseling- and pregnancy-timing, fertility preservation, obstetrics, and oncologic outcomes. One expert clinician for each of 50 major gynecologic oncology centers was invited to participate. Data were entered into a database and statistically analyzed. 74% of questionnaires were complete. The proportion of EOC patients treated with FSS was <10%, 10%-20% and >20% in 70.3%, 24.3% and 5.4% of cases, respectively. Age, fertility preservation desire, histotype, and stage were considered relevant to select patients for a conservative treatment for 64.8...

Research paper thumbnail of Neoadjuvant chemotherapy in high-risk ovarian cancer patients: Role of age

Tumori, Jan 29, 2018

To review a single-center clinical experience with neoadjuvant chemotherapy (NACT) in a populatio... more To review a single-center clinical experience with neoadjuvant chemotherapy (NACT) in a population of frail epithelial ovarian cancer (EOC) patients and investigate the prognostic role of advanced age. We retrospectively reviewed clinical data from 102 advanced EOC patients treated with NACT and presenting high perioperative risk. Patients were divided into 2 groups: group A, including patients aged 70 years or older; and group B, including patients below 70 years old. Univariate and multivariate analyses were performed to compare survival and prognostic factors for survival between the two groups. Forty-two patients (41.2%) were older than 70 years. Elderly patients were more likely to present comorbidities ( p = .0001), poor performance status ( p = .04), and multiple indications for NACT ( p = .03). They showed a reduced response to NACT, since only 64% of elderly patients underwent surgical debulking (98.3% vs 64.3%, p = .001) and, among these, half of them were optimally debulk...

Research paper thumbnail of {"__content__"=>"Early Regenerative Modifications of Human Postmenopausal Atrophic Vaginal Mucosa Following Fractional CO Laser Treatment.", "sub"=>{"__content__"=>"2"}}

Open access Macedonian journal of medical sciences, Jan 25, 2018

Postmenopausal women experience undesired symptoms that adversely affect their quality of life. I... more Postmenopausal women experience undesired symptoms that adversely affect their quality of life. In the recent years, a specific 12 - week fractional CO laser treatment has been introduced, with highly significant relief of symptoms. The aim of this paper is the identification of the early modifications of structural components of atrophic vaginal mucosa induced by laser irradiation, which is responsible for the restorative processes. We investigated by microscopical, ultrastructural and biochemical methods the modifications of the structural components of postmenopausal atrophic vaginal mucosa tissues after 1 hour following a single fractional laser CO application. In one hour, the mucosal epithelium thickens, with the maturation of epithelial cells and desquamation at the epithelial surface. In the connective tissue, new papillae indenting the epithelium with newly formed vessels penetrating them, new thin fibrils of collagen III are also formed in a renewed turnover of components ...

Research paper thumbnail of Fertility preservation in women harboring deleterious BRCA mutations: ready for prime time?

Human reproduction (Oxford, England), 2017

Fertility issues have become critical in the management and counseling of BRCA mutation carriers.... more Fertility issues have become critical in the management and counseling of BRCA mutation carriers. In this setting four points deserve consideration. (1) Women in general lose their ability to conceive at a mean age of 41 years, thus the suggested policy of prophylactic bilateral salpingo-oophorectomy at age 40 for BRCA mutation carriers does not affect the chances of natural pregnancy. Conversely, if the procedure is chosen at 35 years old, oocyte cryopreservation prior to surgery should be considered. (2) Some evidence suggests that ovarian reserve may actually be partly reduced in BRCA mutations carriers and that the mutation may affect ovarian responsiveness to stimulation. However, these findings are still controversial. (3) Breast cancer is not rare before the age of 40 and fertility preservation after diagnosis can be requested in a significant proportion of BRCA mutation carriers. Thus, a policy of oocyte cryopreservation in young healthy carriers deserves consideration. The ...

Research paper thumbnail of Comparison of Laparoscopy and Laparotomy Staging of Early-Stage Ovarian Cancer: A Study with 12-Year Experience

Journal of Minimally Invasive Gynecology

Research paper thumbnail of Sexual Function in Women Suffering From Genitourinary Syndrome of Menopause Treated With Fractionated CO2 Laser

Sexual medicine reviews, Jan 23, 2017

Genitourinary syndrome of menopause (GSM) has a significant impact on the trophism of the genital... more Genitourinary syndrome of menopause (GSM) has a significant impact on the trophism of the genital and lower urinary tracts and can considerably impair sexual function. Fractional CO2 laser has a regenerative effect on vulvovaginal tissue trophism after menopause. To review the available literature on the effect of fractional CO2 laser on the sexual function of postmenopausal women affected by GSM. A database search was carried out using the terms CO2laser, vaginal atrophy, sexual function, dyspareunia, and genitourinary syndrome of menopause and excluding studies using other types of laser or including breast cancer survivors with vulvovaginal atrophy. For statistical analysis, the estimated overall laser effect was computed (when at least two studies were involved) and data type of generic inverse variance was computed using inverse variance as the statistical method, a random-effects model, and the difference in means as an effect measurement. Different methods of evaluating sexua...

Research paper thumbnail of Advances in improving fertility in women through stem cell-based clinical platforms

Expert opinion on biological therapy, 2017

Due to their regenerative ability, stem cells are looked at as a promising tool for improving inf... more Due to their regenerative ability, stem cells are looked at as a promising tool for improving infertility treatments in women. As the main limiting factor in female fertility is represented by the decrease of ovarian reserve, the main goals of stem cell-based clinical platforms would be to obtain in vitro or in vivo neo-oogenesis. Refractory endometrial factor infertility also represents an obstacle for female reproduction for which stem cells might provide novel treatment strategies. Areas covered: A systematic search of the literature was performed on MEDLINE/PubMed database to identify relevant articles using stem-cell based clinical or research platforms in the field of female infertility. Expert opinion: In vitro oogenesis has not so far developed beyond the stage of oocyte-like cells whose normal progression to mature oocytes and ability to be fertilized was not proved. Extensive epigenetic programming of gamete precursors and the complex interactions between somatic and germ ...

Research paper thumbnail of Long-acting recombinant FSH in random start ovarian stimulation protocols for fertility preservation in women with cancer

Acta obstetricia et gynecologica Scandinavica, Jan 6, 2017

The objective of this study was to assess effectiveness and the potential benefits of the use of ... more The objective of this study was to assess effectiveness and the potential benefits of the use of long-acting recombinant follicle-stimulating hormone (FSH) in random-start protocol for fertility preservation in women with cancer. This is a retrospective before and after study performed between February 2013 and December 2015 in women that underwent ovarian hyper-stimulation for oocyte cryobanking using a random start approach. In the first part of the study period, the subjects were treated with daily recombinant FSH whereas in the second part the stimulation was initiated with long-acting recombinant FSH. The primary aim of the study was to compare the number of oocytes stored in the two study periods. 140 women were ultimately selected. Compared to daily recombinant FSH, the use of the long-acting compound was associated with a reduced number of injections (12.5 ± 3.5 vs 16.4 ± 0.3; p<0.001) and a longer duration of stimulation (11.4 ± 1.9 vs 10.6 ± 1.9, p=0.01). Conversely, th...

Research paper thumbnail of Nuchal translucency measurement, free β-hCG and PAPP-A concentrations in IVF/ICSI pregnancies: systematic review and meta-analysis

Prenatal diagnosis, Jan 17, 2017

So far data on the effect of assisted reproductive technologies (ART) on the components of first ... more So far data on the effect of assisted reproductive technologies (ART) on the components of first trimester combined screening for Down syndrome are still controversial. A systematic search of the literature was performed in order to identify the effect of ART, particularly IVF and ICSI with fresh embryo transfer, on the nuchal translucency (NT), free β-hCG and PAPP-A measurements. Moreover, a meta-analysis and a descriptive graphical representation of the ratios between ART and spontaneous pregnancies (controls) values of median of the multiple of median (m0MOM) was performed. Free β-hCG test showed slightly higher values in the ICSI group than controls (RR = 1.09, 95%CI: 1.03-1.16) but not in the IVF group (RR = 1.03, 95%CI: 0.94-1.12). PAPP-A values for IVF/ICSI, IVF and ICSI showed lower values in comparison with controls (RR, 95%CI 0.85, 0.80-0.90; 0.82, 0.74-0.89 and 0.83, 0.79-0.86 respectively). The NT measurement did not show any statistical differences between study groups ...

Research paper thumbnail of Bladder Endometriosis: A Systematic Review of Pathogenesis, Diagnosis, Treatment, Impact on Fertility, and Risk of Malignant Transformation

European urology, Jan 28, 2016

The bladder is the most common site affected in urinary tract endometriosis. There is controversy... more The bladder is the most common site affected in urinary tract endometriosis. There is controversy regarding the pathogenesis, clinical management (diagnosis and treatment), impact on fertility, and risk of malignant transformation of bladder endometriosis (BE). To systematically evaluate evidence regarding the pathogenesis, diagnosis, medical and surgical treatment, impact on female fertility, and risk of malignant transformation of BE. A systematic review of PubMed/Medline from inception until October 2016 was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and was registered in the PROSPERO registry (www.crd.york.ac.uk/prospero; CRD42016039281). Eighty-seven articles were selected for inclusion in this analysis. BE is defined as the presence of endometrial glands and stroma in the detrusor muscle. Ultrasonography is the first-line technique for assessment of BE owing to its accuracy, safety, and cost. Clinical m...

Research paper thumbnail of Thoracic Endometriosis Syndrome: Association With Pelvic Endometriosis and Fertility Status

Journal of Minimally Invasive Gynecology, 2017

To evaluate associations among catamenial pneumothorax, pelvic endometriosis, and fertility statu... more To evaluate associations among catamenial pneumothorax, pelvic endometriosis, and fertility status. Retrospective study (Canadian Task Force classification II-2). Departments of Thoracic Surgery and Obstetrics and Gynecology, San Raffaele Hospital, Milan, Italy. Sixteen females referred to the Department of Thoracic Surgery for treatment of spontaneous pneumothorax between January 2001 and January 2014 and referred to the outpatient clinic for gynecologic follow-up. Thoracoscopy for catamenial pneumothorax and laparoscopy for pelvic endometriosis. Characteristics of the patients, the presence of endometriosis, and their fertility status were statistically analyzed. Pelvic endometriosis was diagnosed in 9 patients (56.3%), but 6 patients did not undergo a laparoscopic procedure to confirm or exclude the disease. Seven of the affected patients (77.8%) had stage III-IV endometriosis. Two-thirds of the patients with pelvic endometriosis who attempted conception conceived spontaneously, as did all of the patients without histopathological confirmation of endometriosis. Thoracic endometriosis syndrome, characterized mainly by catamenial pneumothorax, is a relevant condition in patients affected by endometriosis. However, few previous studies have analyzed this condition from a gynecologic standpoint, in terms of characteristics of endometriosis and fertility status of affected women. Our findings support the presence of a strong association between catamenial pneumothorax and pelvic endometriosis, as well as a minimal effect of catamenial pneumothorax on fertility status, even in the presence of pelvic endometriosis.

Research paper thumbnail of Pregnancy outcome in women with endometriosis achieving pregnancy with IVF

Human Reproduction, 2016

Women with endometriosis who conceive with IVF do not face an increased risk of preterm birth. WH... more Women with endometriosis who conceive with IVF do not face an increased risk of preterm birth. WHAT IS KNOWN ALREADY: The eutopic endometrium of women with endometriosis has been repeatedly shown to present molecular and cellular alterations. On this basis, it has been hypothesized that pregnancy outcome may be altered in affected women. However, to date, available evidence from epidemiological studies is scanty and conflicting. Data tended to be partly consistent only for an increased risk of preterm birth and placenta previa. STUDY DESIGN, SIZE, DURATION: Retrospective matched case-control study of women achieving an IVF singleton pregnancy progressing beyond 12 weeks' gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women achieving IVF singleton pregnancies that progressed beyond 12 weeks' gestation at two infertility units were reviewed. Cases were women with a history of surgery for endometriosis and/or with a sonographic diagnosis of the disease at the time of the IVF cycle. Controls were women without current or past evidence of endometriosis who were matched to cases by age (± 6 months), type of cycle (fresh or frozen cycle) and study period. Male factor and unexplained infertility were the most common diagnoses in the control group. Two hundred and thirty-nine women with endometriosis and 239 controls were selected. The main outcome of the study was the rate of preterm birth (birth < 37 weeks' gestation) regardless of the cause. Secondary analyses were performed for the most common obstetrical complications. MAIN RESULTS AND THE ROLE OF CHANCE: The rate of preterm birth was similar in the two study groups (14% and 14%, respectively, p = 0.89). The rate of live birth and the incidence of hypertensive disorders, gestational diabetes, small and large for gestational age newborns and neonatal problems also did not differ. In contrast, placenta previa was more common in women with endometriosis than controls (6% versus 1%, respectively; p = 0.006): The adjusted odds ratio was 4.8 (95% confidence interval: 1.4-17.2). LIMITATIONS, REASONS FOR CAUTION: As for all observational studies, confounders cannot be totally excluded. Moreover, the retrospective study design exposes the findings to some inaccuracies. For example, the independent role of adenomyosis could not be reliably assessed because this diagnosis is complex and would necessitate a prospective recruitment. Second, the selection of controls may also be a matter of concern because some affected women may have been erroneously included in this group. Third, even if the sample size is significant, it is insufficient for robust subgroup analyses. Finally, it is mandatory to point out that our conclusions are valid for IVF pregnancies only, and specific data from properly designed studies are required to support any inference for natural pregnancies.

Research paper thumbnail of Fertility preservation in women with borderline ovarian tumours

Cancer Treatment Reviews, 2016

Borderline ovarian tumours (BOT) may occur in young women and have an excellent survival rate. Th... more Borderline ovarian tumours (BOT) may occur in young women and have an excellent survival rate. Therefore, there is the obligation to put emphasis on fertility preservation in affected women. On the other hand, it has also been underlined that the disease should be managed with caution because these tumours can relapse and, albeit rare, malignant transformation can also occur. Unfortunately, evidence on fertility preservation in women with BOT is scanty. In this opinion paper, we tried to draw some clinical indications based on the few available studies on the clinical management of BOT and their possible relation with controlled ovarian hyper-stimulation (COH). We ultimately came to the following conclusions: (1) Fertility counselling should become an integral part of the clinical management of women with BOT. Conservative management without pre-surgical counselling may expose women without reasonable chances of future conceptions to undue risks. (2) Despite some epidemiological concerns on the possible relation between COH and BOT, the conservative surgical treatment should be associated to oocyte cryopreservation considering the high risk of recurrence of the disease. (3) Letrozole during COH should be considered to temper the theoretical risk of increased recurrences. (4) Pregnancy should not be delayed in women at low-moderate risk of recurrences. Fertility preservation may be avoided in these women provided that they start active pregnancy seeking early. (5) Albeit experimental, oocytes retrieval from affected ovaries removed at the time of surgery can be considered. Conversely, ovarian cortex cryopreservation is not justified given the possible risks of malignant reseeding.

Research paper thumbnail of Application of failure mode and effect analysis in an assisted reproduction technology laboratory

Reproductive biomedicine online, Jan 24, 2016

Assisted reproduction technology laboratories have a very high degree of complexity. Mismatches o... more Assisted reproduction technology laboratories have a very high degree of complexity. Mismatches of gametes or embryos can occur, with catastrophic consequences for patients. To minimize the risk of error, a multi-institutional working group applied failure mode and effects analysis (FMEA) to each critical activity/step as a method of risk assessment. This analysis led to the identification of the potential failure modes, together with their causes and effects, using the risk priority number (RPN) scoring system. In total, 11 individual steps and 68 different potential failure modes were identified. The highest ranked failure modes, with an RPN score of 25, encompassed 17 failures and pertained to "patient mismatch" and "biological sample mismatch". The maximum reduction in risk, with RPN reduced from 25 to 5, was mostly related to the introduction of witnessing. The critical failure modes in sample processing were improved by 50% in the RPN by focusing on staff t...

Research paper thumbnail of Creation of a neovagina in Rokitansky patients with a pelvic kidney: comparison of long-term results of the modified Vecchietti and McIndoe techniques

Fertility and Sterility, Mar 1, 2010

To evaluate perioperative data and long-term results of Rokitansky patients with a pelvic kidney ... more To evaluate perioperative data and long-term results of Rokitansky patients with a pelvic kidney that underwent the McIndoe and modified Vecchietti procedures. Design: Retrospective descriptive study. Setting: A tertiary referral center for the study and treatment of Rokitansky syndrome. Patient(s): Eleven patients with Rokitansky syndrome. Intervention(s): Two and nine patients, respectively, underwent the McIndoe and Vecchietti modified techniques. Main Outcome Measure(s): Anatomic success was defined as a neovagina R6 cm long allowing easy introduction of two fingers within 6 months postoperatively. Functional success was considered achieved when the patient reported satisfactory sexual intercourse starting from 6 months postoperatively. Result(s): Surgery was performed with no complications in all 11 patients. The mean duration of surgery was 190 AE 14.1 minutes in the first group and 32 AE 6.4 minutes in the second group. At 14 years of follow-up, both patients who underwent McIndoe vaginoplasty had a mean AE SD length and width of 8.2 AE 0.4 cm and 5 cm and negative Schiller's test 24 months postoperatively. At 4 years of follow-up, eight out of the nine patients who underwent the Vecchietti procedure (89%) had a mean AE SD length and width of the neovagina of 7.4 AE 0.6 cm and 4.2 AE 0.5 cm and iodine-positive vaginal-type epithelium coating 100% of the neovagina 24 months postoperatively. Conclusion(s): While appearing to be safe, effective, and with optimal functional results, the modified Vecchietti approach also seems to yield good anatomical and aesthetic results along with shorter surgical and hospitalization times. (Fertil Steril Ò 2010;93:1280-5. Ó2010 by American Society for Reproductive Medicine.

Research paper thumbnail of Use of knockout transgenic mice in the study of endometriosis : insights from mice lacking β2-microglobulin and interleukin-12p40

Fertility and Sterility, 2001

To test the possibility of using transgenic knockout mice in the study of endometriosis and to in... more To test the possibility of using transgenic knockout mice in the study of endometriosis and to investigate specific immunologic aspects of the disease. Experimental blinded study. Academic research center. Thirty-two mice with experimentally induced endometriosis. Endometriosis was induced in 8 beta(2)-microglobulin-deficient BALB/c mice and 7 wild-type BALB/c controls. Similarly, endometriosis was induced in 8 interleukin-12-deficient C57BL/6 mice and in 9 wild-type C57BL/6 controls. Weight and surface area of endometriotic lesions. Total weight and surface area of endometriotic lesions was markedly lower in beta(2)-microglobulin-deficient BALB/c mice than in wild-type BALB/c controls. A slight but statistically insignificant increase in total weight and surface area of lesions was observed in interleukin-12-deficient C57BL/6 mice compared to wild-type C57BL/6 controls. Knockout transgenic mice can be used successfully for the study of endometriosis; however, in these animals, the redundancy of the immunologic cytokine-mediated regulatory mechanisms may lead to compensation from the remaining genome. Results from beta(2)-microglobulin-deficient mice support the critical role of the immune system in the pathogenesis of the disease.

Research paper thumbnail of Risk of miscarriage in women with endometriosis: insights from in vitro fertilization cycles

Fertility and sterility, Aug 16, 2016

To evaluate whether women with endometriosis achieving singleton pregnancies with IVF face an inc... more To evaluate whether women with endometriosis achieving singleton pregnancies with IVF face an increased risk of miscarriage. Matched case-control study. Infertility units. Women achieving singleton pregnancies with the use of IVF were considered. Cases were women with a history of surgery for endometriosis and those who were documented the presence of ovarian endometriomas at the time of the IVF cycle (n = 313). Controls were matched to cases by age (±6 months), type of cycle (fresh or frozen cycle). and study period (n = 313). Retrospective review of women undergoing IVF. Rate of miscarriage before 12 weeks' gestation. The number of miscarriages in women with and without endometriosis was similar, being 48 (15%) and 60 (19%), respectively. The odds ratio of miscarriage in affected women was 0.76 (95% confidence interval 0.50-1.16). The odds ratio adjusted for body mass index (BMI), parity, duration of infertility, and male factor infertility was 0.81 (95% confidence interval 0....

Research paper thumbnail of Mental Representations of Illness in Patients with Gestational Trophoblastic Disease: How Do Patients Perceive Their Condition?

PloS one, 2016

Gestational Trophoblastic Disease comprises a group of benign and malignant disorders that derive... more Gestational Trophoblastic Disease comprises a group of benign and malignant disorders that derive from the placenta. Using Leventhal's Common-Sense Model as a theoretical framework, this paper examines illness perception in women who have been diagnosed with this disease. Thirty-one women diagnosed with Gestational Trophoblastic Disease in a hospital in Italy were asked to complete the Illness Perception Questionnaire-Revised to measure the following: illness Identity, illness opinions and causes of Gestational Trophoblastic Disease. High mean scores were observed in the Emotional representations and Treatment control subscales. A significant difference emerged between hydatidiform mole patients and those with gestational trophoblastic neoplasia on the Identity subscale. A significant correlation emerged between "time since diagnosis" and the Treatment control subscale. This study is the first to investigate illness perception in Gestational Trophoblastic Disease. From...

Research paper thumbnail of Elevated Systemic Levels of Endocannabinoids and Related Mediators Across the Menstrual Cycle in Women With Endometriosis

Reproductive sciences (Thousand Oaks, Calif.), Aug 17, 2016

Cannabinoids and modulators of the endocannabinoid system affect specific mechanisms that are cri... more Cannabinoids and modulators of the endocannabinoid system affect specific mechanisms that are critical to the establishment and development of endometriosis. The aim of this study was to measure the systemic levels of endocannabinoids and related mediators in women with and without endometriosis and to investigate whether such levels correlated with endometriosis-associated pain. Plasma and endometrial biopsies were obtained from women with a laparoscopic diagnosis of endometriosis (n = 27) and no endometrial pathology (n = 29). Plasma levels of endocannabinoids (N-arachidonoylethanolamine [AEA] and 2-arachidonoylglycerol [2-AG]) and related mediators (N-oleoylethanolamine [OEA] and N-palmitoylethanolamine [PEA]), messenger RNA expression of some of their receptors (cannabinoid receptor type 1 [CB1], CB2, transient receptor potential vanilloid type [TRPV1]), and the enzymes involved in the synthesis (N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D [NAPE-PLD]) and degrada...