Ovarian tissue transplantation: 10 years of experience at the Bologna University.

Objective: The efficiency of ovarian tissue transplantation (OTT) was established in terms of ovarian function recovery (95% of cases), number of live births (over 200 worldwide to date) and induction of puberty. Unfortunately, the lack of international registries and the fact that many centers have not yet reported their outcomes, lead to poor knowledge of the exact fertility data. The aim of the study is to describe our experience with OTT to restore ovarian function and fertility. Methods: This study was designed as a single-center, observational, retrospective, cohort study that includes women who underwent OTT between December 2012 and June 2023 at our center. After approval by the oncologist/hematologist, a small fragment of ovarian tissue was thawed and analyzed to detect the presence of micrometastases before OTT. Thawed ovarian tissue was grafted laparoscopically at multiple sites, including the remaining ovary and pelvic side wall (orthotopic transplantation) and/or abdominal wall (heterotopic transplantation). After OTT, ovarian function was monitored by hormonal assay, ultrasound and color Doppler at approximately 4-week intervals. Results: Between December 2012 and June 2023, 30 women performed OTT. Prior to OTT, immunohistochemical and molecular analyses revealed no micrometastases in all thawed ovarian tissue samples. In our series of 30 women, 20 of women were on premature ovarian insufficiency (POI), and the remaining ten cases still had oligomenorrhea and difficulty getting pregnant. Among the women with POI before OTT and at least 6 months follow-up, recovery of endocrine function was observed in all but one woman who underwent orthotopic transplantation (13 of 14 cases), in one out of two women who underwent both orthotopic and heterotopic transplantation (1 of 2 cases) and in all women who underwent heterotopic transplantation (4 of 4 cases). Women who underwent OTT to enhance fertility had no alterations in menstrual cycle and hormonal levels. In total, ten pregnancies were obtained in 25 women, resulting in four live births, two ongoing pregnancies and four spontaneous abortions. Conclusion: Our data can help patients and physicians in their discussions and decisions about the need and possibilities of preserving fertility.

Molecular Signature of Endometrial Cancer with Coexistent Adenomyosis: A Multicentric Exploratory Analysis.

Adenomyosis has been associated with better survival outcomes in women with endometrial cancer. However, although the endometrial cancer patients' risk stratification has been revolutionized by molecular findings, the impact of the molecular signature on the favorable prognosis of endometrial cancer patients with coexistent adenomyosis is unknown. The aim of our study was to compare the prevalence of molecular groups at poor and intermediate prognosis between endometrial cancer patients with and without coexistent adenomyosis. A multicentric, observational, retrospective, cohort study was performed to assess the differences in the prevalence of p53-abnormal expression (p53-abn) and mismatch repair protein-deficient expression (MMR-d) signatures between endometrial cancer patients with and without coexistent adenomyosis. A total of 147 endometrial cancer patients were included in the study: 38 in the adenomyosis group and 109 in the no adenomyosis group. A total of 37 patients showed the MMR-d signature (12 in the adenomyosis group and 25 in the no adenomyosis group), while 12 showed the p53-abn signature (3 in the adenomyosis group and 9 in the no adenomyosis group). No significant difference was found in the prevalence of p53-abn (p = 1.000) and MMR-d (p = 0.2880) signatures between endometrial cancer patients with and without coexistent adenomyosis. In conclusion, the molecular signature does not appear to explain the better prognosis associated with coexistent adenomyosis in endometrial cancer patients. Further investigation of these findings is necessary through future larger studies.

Dienogest alone or dienogest combined with estrogens in the treatment of ovarian endometriomas, that is the question. A retrospective cohort study.

PURPOSE: to compare the effects of Dienogest 2 mg (D) alone or combined with estrogens (D + ethinylestradiol 0.03 mg, D + EE; D + estradiol valerate 1-3 mg, D + EV) in terms of symptoms and endometriotic lesions variations. METHODS: This retrospective study included symptomatic patients in reproductive age with ultrasound diagnosis of ovarian endometriomas. Medical therapy for at least 12 months with D, D + EE or D + EV was required. Women were evaluated at baseline visit (V1) and after 6 (V2) and 12 months (V3) of therapy. RESULTS: 297 patients were enrolled (156 in the D group, 58 in the D + EE group, 83 in the D + EV group). Medical treatment leaded to a significant reduction in size of endometriomas after 12 months, with no differences between the three groups. When comparing D and D + EE/D + EV groups, a significant decrease of dysmenorrhea was detected in the D group than in D + EE/D + EV group. Conversely, the reduction of dysuria was more significative in the D + EE/D + EV groups rather than in the D group. Regarding tolerability, treatment associated side effects were reported by 16.2% patients. The most frequent one was uterine bleeding/spotting, significantly higher in the D + EV group. CONCLUSION: Dienogest alone or associated with estrogens (EE/EV) seems to be equally effective in reducing endometriotic lesions mean diameter. The reduction of dysmenorrhea was more significative when D was administered alone, while dysuria seems to improve more when D is associated with estrogens.

Detection of Non-Hodgkin Lymphoma Within Ovarian Tissue.

This case report describes the detection of non-Hodgkin lymphoma (NHL) within ovarian tissue after cryopreservation. The 27-year-old woman presented no gynecological symptoms such as pelvic pain or abnormal uterine bleeding. During laparoscopy for ovarian tissue cryopreservation, the ovaries appeared markedly modified and some solid content cysts were highlighted. Microscopically the cysts revealed the presence of lymphoid infiltrate, whereas the histological assessment of some fragments of the ovarian cortical tissue revealed no evidence of pathological lymphoid infiltration. This case report describes the presence of pathological lymphoid infiltration in ovarian cysts but not in the cortical tissue of a young woman with secondary NHL. Despite the absence of the positivity in cortical tissue it was recommended to avoid the cryopreserved ovarian tissue transplantation to reduce the risk of reseeding of the malignancy in the woman.

Postoperative morphologic changes of the isthmocele and clinical impact in patients treated by channel-like (360°) hysteroscopic technique.

OBJECTIVE: To evaluate the changes in (1) residual myometrial thickness (RMT), (2) cesarean scar defect (CSD) size, and (3) clinical symptoms, before and after channel-like (360°) hysteroscopic resection for the treatment of CSD. METHODS: A single-center, observational, prospective, cohort study was carried out enrolling all symptomatic patients of childbearing age, diagnosed with CSD and routinely scheduled for channel-like (360°) hysteroscopic resection from July 2020 to July 2021 at the Division of Gynecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Univeristaria di Bologna. University of Bologna, Italy. The primary outcome was the difference in mean RMT before and after the procedure. Secondary outcomes were the differences before and 4 months after the surgery in: (1) CSD size measured by transvaginal ultrasound, (2) visual analog scale (VAS) scores for the symptoms, and (3) abnormal uterine bleeding (AUB) rate. Lastly, patients' satisfaction was assessed by the global impression of improvement (PGI-I) score. RESULTS: We found a significant difference before and after the procedure in: (1) mean RMT (+2.0 mm; P < 0.001); mean size of the CSD (base: +1.6 mm; height: -2.5 mm; transverse diameter: -3.2 mm; volume: -263.7 mm3 ; P < 0.001); (2) mean VAS score for dyspareunia (-5.84; P < 0.001), dysmenorrhea (-8.94; P < 0.001), pelvic pain (-2.94; P < 0.001); (3) AUB rate (91% vs. 3%; P < 0.001). Lastly, the mean PGI-I score ± SD was 1.7 ± 0.9. CONCLUSION: Channel-like (360°) hysteroscopic resection for the treatment of patients with symptomatic CSD may lead to an increase in RMT, decrease in CSD, and improvement of symptoms after the procedure, with high patient satisfaction.

Effects of Pelvic Floor Muscle Physiotherapy on Urinary, Bowel, and Sexual Functions in Women with Deep Infiltrating Endometriosis: A Randomized Controlled Trial.

Background and Objectives: Endometriosis is a chronic and recurrent disease defined as the presence and proliferation of endometrial glands and stroma outside the uterine cavity. It affects up to 6-10% of women of reproductive age and can be classified into superficial, ovarian, and deep infiltrating endometriosis (DIE). Deep infiltrating endometriosis can be associated with pain symptoms and pelvic floor muscle hypertone. Moreover, it may be responsible of bowel, urinary, and sexual dysfunctions with impairment of women's quality of life. Few studies have investigated the role of physiotherapy in women with DIE. Here, we aimed first to evaluate the effects of pelvic floor physiotherapy (PFP) on urinary, bowel, and sexual functions. Secondly, we aimed to evaluate the effects of ultrasound visual feedback during PFP on pelvic floor and subjective modifications in the frequency of sexual intercourse. Materials and Methods: This randomized controlled trial was conducted between June 2018 and December 2019 at our tertiary center. Nulliparous women with DIE and superficial dyspareunia were enrolled. At first examination, levator hiatal area (LHA) assessed with 3D/4D transperineal ultrasound, pain symptoms, urinary, bowel, and sexual functions were evaluated. Then, women were randomly assigned to no intervention (control group) or treatment with five individual sessions of PFP (experimental group), and after four months women underwent a second examination. Urinary, bowel, and sexual functions were assessed with validated questionnaires at first and second examinations. In particular, the Bristol Female Lower Urinary Tract Symptoms questionnaire was used to evaluate urinary symptoms, the Knowles-Eccersley-Scott-Symptom questionnaire to assess the presence of constipation, and the Female Sexual Function Index to investigate sexual function. Study outcomes were the comparisons among groups in terms of differences in actual changes in median of questionnaire scores between first and second examinations. Results: Thirty women (17 in the experimental group and 13 in the control group) completed the study. No significant differences were found between the two groups regarding urinary, bowel, and sexual functions, although women in the experimental group showed a tendency towards an improvement in constipation symptoms. Conclusion: In women with DIE, PFP does not appear to affect urinary, bowel, and sexual functions. Therefore, despite the improvement in superficial dyspareunia, chronic pelvic pain, and PFM relaxation with high treatment satisfaction, women should be informed about the unclear impact of PFP on urinary, bowel, and sexual functions. Larger studies are necessary to further investigate the impact of PFP on these functions.

Corrigendum: Ovarian tissue cryopreservation and transplantation: 20 years experience in Bologna University.

[This corrects the article DOI: 10.3389/fendo.2022.1035109.].

Is preoperative ultrasound tumor size a prognostic factor in endometrial carcinoma patients?

Objective: We aimed to assess the prognostic value of preoperative ultrasound tumor size in EC through a single center, observational, retrospective, cohort study. Methods: Medical records and electronic clinical databases were searched for all consecutive patients with EC, preoperative ultrasound scans available to ad hoc estimate tumor size, and a follow-up of at least 2-year, at our Institution from January 2010 to June 2018. Patients were divided into two groups based on different dimensional cut-offs for the maximum tumor diameter: 2, 3 and 4 cm. Differences in overall survival (OS), disease specific survival (DSS) and progression-free survival (PFS) were assessed among the groups by using the Kaplan-Meier estimator and the log-rank test. Results: 108 patients were included in the study. OS, DSS and PFS did not significantly differ between the groups based on the different tumor diameter cut-offs. No significant differences were found among the groups sub-stratified by age, BMI, FIGO stage, FIGO grade, lymphovascular space invasion status, myometrial invasion, lymph nodal involvement, histotype, and adjuvant treatment. Conclusions: Preoperative ultrasound tumor size does not appear as a prognostic factor in EC women.

Ovarian tissue cryopreservation and transplantation: 20 years experience in Bologna University.

Objective: To report the 20-year experience in ovarian tissue cryopreservation (OTC) and ovarian tissue transplantation (OTT) of the Bologna clinical center (Bologna, Italy). Design: Retrospective cohort study. Patients: 1026 pediatrics and women aged between 2 and 38 years who underwent OTC and OTT between January 2002 to January 2022. Results: Of the 1026 patients, 238 (22.8%) were pediatrics (≤ 17 years, Group 1) and 788 (77.2%) were adult women (range 18-38 years, Group 2). In Group 1, 184 (77.3%) patients had malignant diseases and 54 (22.7%) had non-malignant diseases. In Group 2, 746 (94.7%) patients had malignant diseases and 42 (5.3%) had non-malignant diseases. No real complications were observed during surgery. In all the samples analyzed most of the follicles were in the resting stage, while only a few follicles were growing. In both fresh and thawed samples, follicular density was higher in Group 1 than in Group 2 (p < 0.01). Regardless of age, good preservation of follicles and stroma was observed in fresh and thawed ovarian tissue by histological and immunohistochemical analyses (estrogen and progesterone receptors; Ki67 and Bcl2 markers; TUNEL). To date, out of 1026 total women, 812 (79.1%) had their tissue stored. Sixty-eight (6.6%) patients died from their primary disease. Twenty-four (2.3%) women performed 33 OTTs between December 2011 and January 2022. Restoration of menstruation was observed in 15 out of 17 menopausal women. Six pregnancies were achieved, two hesitated in abortion and four in the birth of healthy babies. Conclusion: OTC is the only fertility preservation technique applicable in pre-pubertal/pediatrics and in adult patients when stimulation for oocytes/embryos cryopreservation is not possible. The reported data can help future patients and physicians in their discussions and decisions about the need and possibilities of preserving ovarian function.

3D Patient-Specific Virtual Models for Presurgical Planning in Patients with Recto-Sigmoid Endometriosis Nodules: A Pilot Study.

Background and Objective: In recent years, 3D printing has been used to support surgical planning or to guide intraoperative procedures in various surgical specialties. An improvement in surgical planning for recto-sigmoid endometriosis (RSE) excision might reduce the high complication rate related to this challenging surgery. The aim of this study was to build novel presurgical 3D models of RSE nodules from magnetic resonance imaging (MRI) and compare them with intraoperative findings. Materials and Methods: A single-center, observational, prospective, cohort, pilot study was performed by enrolling consecutive symptomatic women scheduled for minimally invasive surgery for RSE between November 2019 and June 2020 at our institution. Preoperative MRI were used for building 3D models of RSE nodules and surrounding pelvic organs. 3D models were examined during multi-disciplinary preoperative planning, focusing especially on three domains: degree of bowel stenosis, nodule's circumferential extension, and bowel angulation induced by the RSE nodule. After surgery, the surgeon was asked to subjectively evaluate the correlation of the 3D model with the intra-operative findings and to express his evaluation as "no correlation", "low correlation", or "high correlation" referring to the three described domains. Results: seven women were enrolled and 3D anatomical virtual models of RSE nodules and surrounding pelvic organs were generated. In all cases, surgeons reported a subjective "high correlation" with the surgical findings. Conclusion: Presurgical 3D models could be a feasible and useful tool to support surgical planning in women with recto-sigmoidal endometriotic involvement, appearing closely related to intraoperative findings.

Impact of the COVID-19 pandemic on ovarian tissue cryopreservation planning in the Bologna clinical center.

Introduction: Treatment of patients with COVID-19 has been a priority by competing with the treatment of any other disease due to limited hospital resources. The current pandemic situation has focused the attention of healthcare providers around the world away from all other non-emergency health problems, including oncofertility. The aim of the study was to evaluate the repercussions of the COVID-19 pandemic on the activity levels of ovarian tissue cryopreservation (OTC) in the our center. Methods: The study analyzed the number of patients treated for OTC in our center during three periods: pre-pandemic period: March 2019-February 2020, pandemic period: March 2020-February 2021 and post-pandemic period: March 2021-February 2022. Results: In our center routine hospital operation was completely reorganized, allowing only urgent interventions. Continuing to urgently preserve fertility during the pandemic required rapid changes to our standard practices for the care of these vulnerable patients. Despite the modifications, there was no difference in the number of OTC performed among the periods analyzed. Similarly, the number of patients who did not perform OTC was the same over the three years analyzed. Discussion: Despite the local and national restructuring of care to conserve resources and protect the community, it is significant to continue offering fertility-sparing treatment to cancer patients. This emphasis on the importance of preserving fertility despite the pandemic further highlights the essential and urgent nature of this procedure.

Clinical Characteristics of Patients with Endometrial Cancer and Adenomyosis.

A better endometrial cancer (EC) prognosis in patients with coexistent adenomyosis has been reported. Unfortunately, it is still unclear if this better prognosis is related to a more favorable clinical profile of adenomyosis patients. We aimed to evaluate differences in the clinical profiles of EC patients with and without adenomyosis. A systematic review and meta-analysis was performed by searching seven electronics databases for all studies that allowed extraction of data about clinical characteristics in EC patients with and without adenomyosis. Clinical characteristics assessed were: age, Body Mass Index (BMI), premenopausal status, and nulliparity. Mean difference in mean ± standard deviation (SD) or odds ratio (OR) for clinical characteristics between EC patients with and without adenomyosis were calculated for each included study and as a pooled estimate, and graphically reported on forest plots with a 95% confidence interval (CI). The Z test was used for assessing the overall effect by considering a p value < 0.05 as significant. Overall, eight studies with 5681 patients were included in the qualitative analysis, and seven studies with 4366 patients in the quantitative analysis. Pooled mean difference in mean ± SD between EC women with and without adenomyosis was -1.19 (95% CI: -3.18 to 0.80; p = 0.24) for age, and 0.23 (95% CI: -0.62 to 1.07; p = 0.60) for BMI. When compared to EC women without adenomyosis, EC women with adenomyosis showed a pooled OR of 1.53 (95% CI: 0.92 to 2.54; p = 0.10) for premenopausal status, and of 0.60 (95% CI: 0.41 to 0.87; p = 0.007) for nulliparity. In conclusion, there are not significant differences in clinical characteristics between EC patients with and without adenomyosis, with the exception for nulliparity. Clinical features seem to not underlie the better EC prognosis of patients with adenomyosis compared to patients without adenomyosis.

Long-Term Medical Therapy after Laparoscopic Excision of Ovarian Endometriomas: Can We Reduce and Predict the Risk of Recurrence?

OBJECTIVES: Up to 32% of women experience anatomic recurrence after conservative surgery for endometriomas, while pain recurs in 10-40% of cases. Long-term postoperative hormonal therapy is recommended to prevent disease recurrence. We evaluated the efficacy of long-term therapy with estroprogestins (EPs) or progestins (Ps) in preventing endometrioma recurrence, as identifiable cysts and subjective symptoms, after laparoscopic excision. DESIGN: This retrospective cohort study included 375 women submitted to laparoscopic endometrioma excision. Women were followed up at 6 and 12 months and then yearly after surgery. Based on postoperative medical therapy, women were divided into 4 groups: nonusers, cyclic EP users, continuous EP users, and progestogen users. Materials, Setting, Methods: Anamnestic and anthropometric characteristics were collected as well as clinical and surgical data. Gynecological examination, and transvaginal and transabdominal ultrasound scans were performed. Pain (numerical rating score >5) and endometrioma recurrence at ultrasound (ovarian cyst with typical sonographic features ≥10 mm in mean diameter) were recorded at each examination. The reoperation rate in women with recurrence was investigated. RESULTS: The median follow-up was 3.7 years with a maximum of 16.7 years. Most patients used EPs (119 cyclic and 61 continuous users), 95 used P, and 100 were nonusers. In 135 women (36%), endometriotic cyst recurrence was diagnosed, with a mean diameter of 18.7 ± 10.8 mm (range 10-55 mm). The median recurrent cyst-free time was 7.9 years (95% CI 5.8-10.8). Dysmenorrhea was the first symptom to reappear, affecting 162 patients (43.2%). Upon multivariable regression analysis, continuous users had a lower risk of relapse (OR 0.56, 95% CI 0.32-0.99), in terms of both cysts and symptom recurrence, than patients who received no medications. The reoperation rate was 16.2%. LIMITATIONS: The main limitation of this study is its retrospective design. Also, women switching therapies throughout the follow-up period were sorted into one of the study groups based on the longest treatment taken, without considering the discontinuation rates. CONCLUSIONS: Long-term EPs, administered in a continuous regimen and starting immediately after conservative surgery for endometriomas, seem to reduce the disease recurrence risk.

Uterine Fundus Remodeling after Hysteroscopic Metroplasty: A Prospective Pilot Study.

The septate uterus is the most common congenital uterine malformation and is treated by hysteroscopic metroplasty. There are few studies on the fundal uterine changes that occur after surgery. We designed a pilot prospective observational study to evaluate by three-dimensional transvaginal ultrasound (3D-TVS) the changes not only of the internal fundal uterine profile, but also of the external one, after hysteroscopic metroplasty. Sixty women who underwent hysteroscopic metroplasty for partial or complete uterine septum (U2a and U2b subclasses of ESHRE/ESGE classification) were enrolled. We performed 3D-TVS after surgery confirming optimal removal of the septum. However, at ultrasound follow-up after three months, we observed a significant increase (p < 0.001) in the residual septum (Zr) (3.7 mm (95% CI: 3.1-4.4)), the myometrial wall thickness (Y) (2.5 mm (95% CI: 2.0-3.0)) and the total fundal wall thickness (Y + Zr) (6.2 mm (95% CI: 5.5-6.9)). Forty-three patients (72%) required a second step of hysteroscopic metroplasty. Moreover, the shape of uterine fundus changed in 58% of cases. We actually observed a remodeling of the uterine fundus with modifications of its external and internal profiles. Therefore, we propose to always perform a second ultrasound look at least three months after the metroplasty to identify cases that require a second- step metroplasty.

Comparison of Hysteroscopic Cesarean Scar Defect Repair with 26 Fr Resectoscope and 16 Fr Mini-resectoscope: A Prospective Pilot Study.

STUDY OBJECTIVE: Several studies have been published on hysteroscopic treatment of cesarean scar defect using the 26 Fr resectoscope. This study compared the effects of the 26 Fr resectoscope with those of the 16 Fr mini-resectoscope in terms of efficacy, safety profile, and peri- and postoperative complications. DESIGN: A prospective cohort study. SETTING: Tertiary care university hospital (S. Orsola-Malpighi, Bologna, Italy). PATIENTS: Three hundred and nine women having symptoms and with a cesarean scar defect diagnosis were divided into 2 groups according to a temporal criterion: from March 2012 to March 2015, 155 consecutive women (control group) underwent isthmoplasty with the 26 Fr resectoscope (Karl Storz, Tuttlingen, Germany), whereas from April 2015 to March 2018, 154 consecutive women (study group) underwent isthmoplasty with the 16 Fr mini-resectoscope (Gubbini system, Tontarra Medizintechnik, Tuttlingen, Germany). INTERVENTIONS: One hundred and fifty-five women (control group) underwent isthmoplasty with the 26 Fr resectoscope, and 154 women (study group) underwent isthmoplasty with the 16 Fr mini-resectoscope. The so-called "channel-like" 360° endocervical resection technique was applied. MEASUREMENTS AND MAIN RESULTS: The isthmoplasty time with the 2 resectoscopes, excluding cervical dilatation, was similar (p = .25), whereas the overall surgical time was shorter in the case of the mini-resectoscope. The use of the 16 Fr mini-resectoscope was significantly associated with a reduced volume of distension medium used (p <.001) and a lower fluid absorption (p <.001). A significant increase (p = .01) in postoperative complications in the control group (9/155; 5.8%) compared with the study group (1/154; 0.7%) was also found. No significant reduction in discharge time was observed between the 2 groups (p = .13). Patient satisfaction immediately after surgery was significantly higher (p <.001) in the study group than in the control group. CONCLUSION: Isthmoplasty with a 16 Fr mini-resectoscope seems to be as effective as isthmoplasty with a 26 Fr resectoscope in reducing postmenstrual abnormal uterine bleeding and suprapubic pelvic pain. It is associated with a significant reduction in overall surgical time owing to the non-necessity of performing cervical dilatation. The 16 Fr mini-resectoscope facilitates surgery in small anatomical spaces such as the cervical canal and reduces the complication rate linked to blind maneuvers not respecting the uterine anatomy.

Description of the Follicular Fluid Cytokine and Hormone Profiles in Human Physiological Natural Cycles.

PURPOSE: Exogenous gonadotrophins administration during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles could significantly alter the endogenous follicular regulation system and could influence oocyte quality. The analysis of the follicular fluid (FF) cytokine and hormone profiles in physiological natural cycles is crucial to appreciate the role of FF milieu on follicle development. So far, the FF cytokine profile has been analyzed only in controlled ovarian stimulation cycles and in modified natural cycles. Our study defines, in physiological natural cycles, the cytokine and hormone profiles of individual FF aspirated from antral follicles. METHODS: A total of 203 FFs obtained from 83 women with regular menstrual cycles undergoing ovarian tissue cryopreservation were analyzed: 115 FFs from Group 1 (10 to 29 years of age) and 88 FFs from Group 2 (30 to 40 years of age). In individual FF, 27 cytokines were measured with xMAP technology, and progesterone, estrone, estradiol, testosterone, androstenedione concentrations were determined by liquid chromatography-tandem mass spectrometry. RESULTS: FF hormone profiles were not different in follicular and luteal phase, suggesting that FF hormones are regulated independently of the endogenous gonadotrophins-possibly because 74% of the punctured follicles, which were ≤6 mm, did not require cyclic pituitary function. The follicle size was influenced not only by the FF cytokine profile but also by the FF hormone profile, both of which are dependent on age. MAIN CONCLUSIONS: In physiological natural cycles, FF hormones seems to be regulated independently of the endogenous gonadotropins. Age influences FF hormone and cytokine profiles and the compelling relationship between FF hormones and FF cytokines could influence the follicle development.

Fertility Sparing Treatment of Endometrial Cancer with and without Initial Infiltration of Myometrium: A Single Center Experience.

Endometrial cancer (EC) is the fourth largest female cancer in Europe and North America. In 5% of cases, the diagnosis is made in women who wish to become pregnant. In our retrospective study, we reported our experience about fertility sparing treatment of G1 endometrioid endometrial cancer (G1 EEC) or atypical endometrial hyperplasia/endometrial intraepithelial neoplasm (AEH/EIN) in young women desiring pregnancy treated in our Center. Conservative treatment was based on operative hysteroscopy and hormone therapy with megestrol acetate (160 mg/die for 9 months). For the first time we included women with G1 EEC with minimal myometrial infiltration. The minimum follow-up period was two years and consisted of serial outpatient hysteroscopies with endometrial biopsies. Among the 36 women with G1 EEC we observed one case of disease persistence and four recurrences and four recurrences among the 46 women diagnosed with AEH/EIN. To date, 35 live births were obtained in both groups. Our results advance the hypothesis that conservative treatment can represent a safe and feasible alternative to propose to young women with desire for pregnancy. Further randomized and multicentric studies are needed to arrive at unambiguous and standardized guidelines on the surgical and medical treatment of young women with EEC or AEH/EIN.

Adenomyosis and endometriosis in adolescents and young women with pelvic pain: prevalence and risk factors.

AIM: To evaluate the prevalence of ultrasound diagnosis of adenomyosis and endometriosis in young women complaining of pelvic pain and to find the symptoms and clinical characteristics associated with these diseases in young women. METHODS: Cross-sectional study, including 100 young women (14-24 years) with a history of chronic pelvic pain. Women were asked detailed medical hystory and pain symptoms scores (Visual Analogue Scale) and underwent gynecological examination and ultrasound evaluation. RESULTS: The prevalence of endometriosis and adenomyosis in young women amounted to 25.0% and 46.0%, respectively. A significant correlation was found between ovarian endometriosis and adenomyosis. Dysmenorrhea and dyspareunia were risk factors for adenomyosis. Dyschezia, dyspareunia, chronic pelvic pain, presence of sonographic soft markers suggestive of pelvic adhesions, being a worker and having a previous surgery were risk factors for endometriosis. Young women (20-24 years) had a higher incidence of both adenomyosis and endometriosis than adolescents (14-19 years). CONCLUSIONS: Our outcomes strengthen the hypothesis of a progressive and common course of the natural history of endometriosis, which initially may manifest with symptoms, then with signs of pelvic adhesions and finally as adenomyosis, ovarian endometriomas or deep infiltrating endometriosis.

Transperineal Ultrasound Visual Feedback Assisted Pelvic Floor Muscle Physiotherapy in Women With Deep Infiltrating Endometriosis and Dyspareunia: A Pilot Study.

A prospective study with the aim to evaluate the effects of pelvic floor physiotherapy was conducted among women with deep infiltrating endometriosis (DIE) and associated dyspareunia. At initial evaluation superficial and deep dyspareunia were assessed using a numerical rating scale, and levator hiatus area (LHA) was assessed with 3-D/4-D transperineal ultrasound. Women underwent five individual sessions of ultrasound visual feedback assisted pelvic floor physiotherapy. One month after the therapy, dyspareunia and LHA were reassessed and compared with pre-therapy data. Pelvic floor physiotherapy seems to improve both superficial and deep dyspareunia and pelvic floor muscle relaxation in women with DIE.