Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: A Single-Institution Experience and a Review of the Literature.

OBJECTIVES: The aim of this study was to evaluate the role of neoadjuvant chemotherapy (NACT) in advanced ovarian carcinoma patients unable to undergo a complete resection during primary debulking surgery. METHODS: From February 2005 to October 2015, all consecutive cases of advanced-stage epithelial ovarian carcinoma at the University of Bari were retrospectively recorded. Of them, patients treated with NACT were collected. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors of survival. RESULTS: Seventy-eight women with advanced-stage epithelial ovarian carcinoma were treated with NACT. On univariate analysis, age (p = 0.003), CA-125 serum level (0.001), response to NACT (p < 0.0001), stage of disease (p = 0.011) and optimal debulking surgery (p < 0.0001) were found to be important prognostic factors related to survival. However, on multivariate analysis, age, response to NACT, CA-125 serum level and optimal debulking surgery remained as independent poor prognostic factors for survival. The median overall and disease-free survival were 31 and 12 months, respectively. CONCLUSIONS: NACT does not compromise survival in patients with stage IIIC and IV ovarian cancer compared to patients treated with primary surgery. Prospective randomized trials comparing NACT to conventional treatment are needed to determine the quality of life and cost/benefit outcomes for women presenting advanced epithelial ovarian cancer.

The new robotic TELELAP ALF-X in gynecological surgery: single-center experience.

BACKGROUND: To evaluate the safety and feasibility of the new robotic TELELAP ALF-X platform in a heterogeneous series of gynecological procedures. METHODS: Between September 2013 and May 2014, 146 patients were enrolled in this Phase II study trial. Patients with presumed benign or borderline adnexal disease, and benign and early stage malignant uterine disease were prospectively included. RESULTS: Median age was 52 years (range 19-79 years), and median BMI was 23.7 (range 17.3-34.0 kg/m(2)). Sixty-two patients (32.5%) underwent mono/bilateral salpingo-oophorectomy or cyst removal (Group A), four patients (2.7%) myomectomy (Group B), 46 patients (31.5%) total hysterectomy (Group C), and 34 (23.3%) endometrial cancer staging (Group D). Median docking time was 7 min (range 3-36). Median OT was 35 min (range 17-145) in the Group A, 40 min (range 10-50) in the Group B, 133 min (range 58-320) in the Group C, and 160 min (range 69-290) in the Group D. Reduction in OT over the study period for hysterectomy (p < 0.001) and adnexal surgery (p < 0.002) was observed. We registered two laparoscopic conversion (3.2%) in the Group A and two (4.3 %) in the Group C. In the Group D, we showed one (2.9%) laparoscopic and two (5.8%) laparotomic conversions. One patient (2.17%) in the Group C was readmitted in the early postoperative period for severe vaginal bleeding. CONCLUSIONS: We report the first series of a novel robotic approach for the treatment of various gynecological conditions. When performed by experienced minimally invasive surgeons, TELELAP ALF-X is feasible and safe. Further studies are mandatory to define the benefits, advantages, and costs of this new robotic approach with respect to others minimally invasive approaches.

Ulipristal acetate versus leuprolide acetate for uterine fibroids.

BACKGROUND: The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear. METHODS: In this double-blind noninferiority trial, we randomly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate (at a dose of either 5 mg or 10 mg) or once-monthly intramuscular injections of leuprolide acetate (at a dose of 3.75 mg). The primary outcome was the proportion of patients with controlled bleeding at week 13, with a prespecified noninferiority margin of -20%. RESULTS: Uterine bleeding was controlled in 90% of patients receiving 5 mg of ulipristal acetate, in 98% of those receiving 10 mg of ulipristal acetate, and in 89% of those receiving leuprolide acetate, for differences (as compared with leuprolide acetate) of 1.2 percentage points (95% confidence interval [CI], -9.3 to 11.8) for 5 mg of ulipristal acetate and 8.8 percentage points (95% CI, 0.4 to 18.3) for 10 mg of ulipristal acetate. Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate, 5 days for those receiving 10 mg of ulipristal acetate, and 21 days for those receiving leuprolide acetate. Moderate-to-severe hot flashes were reported for 11% of patients receiving 5 mg of ulipristal acetate, for 10% of those receiving 10 mg of ulipristal acetate, and for 40% of those receiving leuprolide acetate (P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate). CONCLUSIONS: Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes. (Funded by PregLem; ClinicalTrials.gov number, NCT00740831.).

Telelap Alf-X-Assisted Laparoscopy for Ovarian Cyst Enucleation: Report of the First 10 Cases.

This prospective single-institutional clinical trial sought to assess the safety and feasibility of laparoscopic benign ovarian cyst enucleation with a novel robotic-assisted laparoscopic system. Here we report a series of 10 patients treated using the Telelap ALF-X system in the first clinical application on patients at the Division of Gynecologic Oncology, Catholic University of the Sacred Heart of Rome. The primary inclusion criterion was the presence of monolateral ovarian cyst without a preoperative assessment suspicious for malignancy. Intraoperative data, including docking time, operative time, estimated blood loss, intraoperative and perioperative complications, and conversion to either standard laparoscopy or laparotomy, were collected. The cysts were removed with an ovary-sparing technique with respect to conservative surgical principles. The median operative time was 46.3 minutes, and patients without postoperative complications were discharged at 1 or 2 days after the procedure. Telelap ALF-X laparoscopic enucleation of benign ovarian cysts with an ovary-sparing technique is feasible, safe, and effective; however, more clinical data are needed to determine whether this approach can offer any other benefits over other minimally invasive surgical techniques.

Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial.

BACKGROUND: Carboplatin plus paclitaxel administered every 3 weeks is standard first-line chemotherapy for patients with advanced ovarian cancer. A weekly paclitaxel schedule combined with carboplatin every 3 weeks prolonged progression-free survival and overall survival in a Japanese phase 3 trial. The aim of our study was to assess whether a weekly schedule of carboplatin plus paclitaxel is more effective than the same drugs given every 3 weeks. METHODS: We did a multicentre, randomised, phase 3 study at 67 institutions in Italy and France. Women with FIGO stage IC-IV ovarian cancer, an ECOG performance status of 2 or lower, and who had never received chemotherapy were randomly allocated in a 1:1 ratio to receive either carboplatin (AUC 6 mg/mL per min) plus paclitaxel (175 mg/m(2)) every 3 weeks for six cycles or carboplatin (AUC 2 mg/mL per min) plus paclitaxel (60 mg/m(2)) every week for 18 weeks. Randomisation was done by computer-based minimisation, stratified by centre, residual disease after surgery, and ECOG performance status. The study was not blinded. Coprimary endpoints were progression-free survival and quality of life (assessed by the Functional Assessment of Cancer Therapy Ovarian Trial Outcome Index [FACT-O/TOI] score), and analysis was by modified intention to treat. This report presents the final analysis. The study is registered with ClinicalTrials.gov, number NCT00660842. FINDINGS: 822 patients were enrolled into the study between Nov 20, 2008, and March 1, 2012; 12 withdrew their consent immediately after randomisation and were excluded, and 810 were eligible for analysis. 404 women were allocated treatment every 3 weeks and 406 were assigned to the weekly schedule. After median follow-up of 22·3 months (IQR 16·2-30·9), 449 progression-free survival events were recorded. Median progression-free survival was 17·3 months (95% CI 15·2-20·2) in patients assigned to treatment every 3 weeks, versus 18·3 months (16·8-20·9) in women allocated to the weekly schedule (hazard ratio 0·96, 95% CI 0·80-1·16; p=0·66). FACT-O/TOI scores differed significantly between the two schedules (treatment-by-time interaction p<0·0001); with treatment every 3 weeks, FACT-O/TOI scores worsened at every cycle (weeks 1, 4, and 7), whereas for the weekly schedule, after transient worsening at week 1, FACT-O/TOI scores remained stable. Fewer patients assigned to the weekly group than those allocated treatment every 3 weeks had grade 3-4 neutropenia (167 [42%] of 399 patients vs 200 [50%] of 400 patients), febrile neutropenia (two [0·5%] vs 11 [3%]), grade 3-4 thrombocytopenia (four [1%] vs 27 [7%]), and grade 2 or worse neuropathy (24 [6%] vs 68 [17%]). Three deaths during the study were attributed to chemotherapy; two women died who were allocated treatment every 3 weeks and one death was recorded in the group assigned the weekly regimen. INTERPRETATION: A weekly regimen of carboplatin and paclitaxel might be a reasonable option for first-line treatment of women with advanced ovarian cancer. FUNDING: None.

Placing mitochondrial DNA mutations within the progression model of type I endometrial carcinoma.

Mitochondrial DNA (mtDNA) mutations have been described in almost all types of cancer. However, their exact role and timing of occurrence during tumor development and progression are still a matter of debate. A Vogelstein-like model of progression is well established for endometrial carcinoma (EC), however, mtDNA has been scarcely investigated in these tumors despite the fact that mitochondrial biogenesis increase has been shown to be a hallmark of type I EC. Here, we screened a panel of 23 type I EC tissues and matched typical hyperplasia for mutations in mtDNA and in four oncosupressors/oncogenes, namely PTEN, KRAS, CTNNB1 and TP53. Overall, mtDNA mutations were identified in 69% of cases, while mutational events in nuclear genes occurred in 56% of the cases, indicating that mtDNA mutations may precede the genetic instability of these genes canonically involved in progression from hyperplasia to tumor. Protein expression analysis revealed an increase in mitochondrial biogenesis and activation of oxidative stress response mechanisms in tumor tissues, but not in hyperplasia, in correlation with the occurrence of pathogenic mtDNA mutations. Our results point out an involvement of mtDNA mutations in EC progression and explain the increase in mitochondrial biogenesis of type I EC. Last, since mtDNA mutations occur after hyperplasia, their potential role in contributing to genetic instability may be envisioned.

The use of different size-hysteroscope in office hysteroscopy: our experience.

PURPOSE: To evaluate the successful rate and patient acceptance of different-sized hysteroscope in office hysteroscopy. METHODS: We retrospectively evaluated 900 office hysteroscopy performed in ambulatory setting using three different hysteroscopes: 5 mm Hamou II (n = 300), 5 mm Bettocchi (n = 300) and 4 mm Bettocchi (n = 300). Endpoints of our study were the successful rate of hysteroscopy, the eventual side effects/complication and the pain intensity experience from the patients using visual analog scale (VAS). RESULTS: Use of 4 mm Bettocchi leads to a higher rate of successfully performed hysteroscopy (99%, n = 297) and statistically significant when compared to the 5 mm Hamou (95%, n = 285) and to the 5 mm Bettocchi (96%, n = 288) (4 mm Bettocchi vs. 5 mm Bettocchi p < 0.05; 4 mm Bettocchi vs. 5 mm Hamou II p < 0,001; 5 mm Bettocchi vs. 5 mm Hamou II ns). Moreover, the VAS score was higher using 5 mm Hamou II (5.72 ± 1.99) and statistically significant when compared to the 4 mm Bettocchi (3.06 ± 2.14) and to the 5 mm Bettocchi (4.27 ± 1.88) (A vs. B p < 0.05; A vs. C p < 0.001; B vs. C p < 0.001). CONCLUSIONS: Our result suggests that the hysteroscope size plays a pivotal role in the acceptance and for the success of office hysteroscopy.

GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET).

Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in "in Vitro" Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH) agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.

Carcinosarcoma of the ovary: analysis of 13 cases and review of the literature.

OBJECTIVES: The aim of this study was to evaluate our experience with patients affected by ovarian carcinosarcoma. PATIENTS AND METHODS: During a 16-year period, data on 13 patients with ovarian carcinosarcoma were collected. They were obtained from hospital charts and follow-up visits. Survival curves were estimated by the Kaplan-Meier method and compared using the log-rank test. All tests were two-tailed with p values < 0.05 considered significant. RESULTS: Our study was conducted on 13 patients with ovarian carcinosarcoma referred to our unit, during an observation time of about 16 years (March 1994 to October 2010). An improved survival was observed in patients treated with optimal cytoreductive surgery with residual tumors <2 cm (30 vs. 5 months; p = 0.042). All patients underwent adjuvant chemotherapy based on the combination of cisplatin, epirubicin and ifosfamide (PEI) and taxol and carboplatin (TAX-CBDCA) regimen. Overall survival of the patient population was 17 months. CONCLUSIONS: Similarly to data published in the literature, we observed that malignant mixed mullerian ovarian tumors are very aggressive and are usually diagnosed at an advanced age and at an advanced stage of disease. Therefore, due to the rarity of the tumor we would like to add our series to those already published in the literature, although our treatment recommendations are actually based upon retrospective studies with a small patient population.

Central nervous system metastases from epithelial ovarian cancer: prognostic factors and outcomes.

OBJECTIVES: To analyze the clinicopathological characteristics and prognostic factors associated with survival in patients with central nervous system (CNS) metastases from epithelial ovarian cancer. METHODS: Twenty patients with CNS involvement from ovarian carcinoma were evaluated in this retrospective study; their features and survivals were analyzed using Kaplan-Meier and log-rank test methods. RESULTS: The incidence of CNS metastases was 5%, among 400 patients with ovarian cancer treated in our single institution. The median age at diagnosis of the ovarian cancer was 55 years. The median interval to the brain involvement and the median survival were 33 and 18 months, respectively. Prognostic factors associated with survival were the International Federation of Gynecology and Obstetrics stage, the surgical resection, the multimodal treatment, and the response after the therapy of the brain metastases. CONCLUSIONS: Brain involvement from ovarian cancer is uncommon but is increasing in incidence. Although the prognosis is usually poor, a multimodal approach can result in a long-term remission of the metastases and in an improvement of the overall survival.

Oocyte morphological abnormalities in overweight women undergoing in vitro fertilization cycles.

The effect of elevated body mass index (BMI) on the oocyte quality was investigated in women undergoing in vitro fertilization (IVF) cycles. A total of 268 patients classified on the basis of BMI subject to the first reproductive treatment were included in this study: the normal weight (NW) group consisted of 160 patients with BMI 19-24.9 kg/m(2) and the overweight (OW) group consisted of 108 patients with BMI ≥ 25 kg/m(2). All women were treated with a standard long luteal protocol. The oocyte features were classified as extracytoplasmic or cytoplasmic abnormalities. Outcomes were oocyte morphology, embryo quality, fertilization and implantation rates, and the ovarian response to stimulation. A higher percentage of oocytes with granular cytoplasm was found in women with BMI ≥ 25 (p = 0.04). However, percentages of mature, immature oocytes and germinal vesicle were similar in both groups. No differences were found in fertilization and cleavage rates and percentages of embryo quality. The implantation rate (p < 0.001) was significantly lower in the OW group than in the NW group. The amount of gonadotrophins was significantly higher in OW group (p = 0.003). These findings suggest that the poor reproductive outcome of obese women is influenced by the release of ova with reduced fertilization potential.

A phase 2 multicenter study of irinotecan and cisplatinum as neoadjuvant treatment in patients with locally advanced cervical cancer.

HYPOTHESIS: To evaluate efficacy and safety of a neoadjuvant treatment with irinotecan and cisplatin [cis-diamminedichloroplatinum(II); CDDP] in patients with locally advanced cervical cancer. METHODS: A phase 2 study was conducted at 13 centers located in Italy. Eighty-seven were enrolled between 2000 and 2003. Patients received irinotecan 175 mg/m2 on day 1 every 3 weeks followed by CDDP 80 mg/m2. Each patient was to receive 3 cycles of treatment. Tumor response was to be evaluated by magnetic resonance imaging 3 weeks after the end of the third cycle. At the end of therapy, all patients were to be examined for radical surgery. RESULTS: Of 71 patients included in the primary analysis, 9 (12.7%) showed a complete response; and 43 (60.6%), a partial response for an overall response rate of 73.2% (95% confidence interval [CI], 61.4%-83.1%). Complete pathological responses were observed in 13.6% of the patients (95% CI, 7.0%-23.0%). Overall survival rate at 4 years was 87.0% (95% CI, 79.5%-94.5%).There were no study-related deaths. Most common adverse events were alopecia in 76 patients (87.4%) and gastrointestinal disorders in 79 patients (90.8%). Serious adverse events were vomiting in 18 patients (20.7%), nausea in 14 (16.1%), diarrhea in 8 (9.2%), and neutropenia in 50 (57.5%). A total of 3 patients (3.4%) were discontinued from the study owing to the occurrence of 1 or more serious adverse event. CONCLUSIONS: Irinotecan and CDDP as neoadjuvant chemotherapy in locally advanced cervical cancer showed a promising response rate. These data warrant confirmation with a phase 3 study.

Carcinosarcoma of the vulva: a case report.

Carcinosarcoma is a well-recognized tumor even if it is an uncommon entity. Neoplasms usually occur in the oral cavity, pharynx, esophagus, larynx and skin, and have been rarely documented in the female genital tract. This case reports a patient with a diagnosis of vulvar carcinosarcoma that has been treated with radical vulvectomy and a left inguinal lymphadenectomy but she died two months later of progressive disease. Because of the extreme rarity and severe prognosis of the tumor, we believe that this is a useful addition to the literature and might serves as a reminder to physicians that a multidisciplinary approach for management should be undertaken for treatment.

Impact of chronic viral diseases on semen parameters.

The aim of this study was to assess the effect of human immunodeficiency virus (HIV), hepatitis C (HCV) and B (HBV) virus infection on semen parameters. Semen samples were obtained from 27 HCV, 34 HIV, 30 HBV and 41 HCV-HIV-seropositive patients and compared with those of a control population of healthy seronegative subjects. Tests for detection of HIV, HCV and HBV were performed on seminal samples. The sperm concentration was significantly decreased in HCV- and HBV-seropositive males compared to that of controls (P < 0.001). The mean sperm motility (a + b) was significantly decreased in HCV- and HBV-seropositive (P < 0.001) and in HCV-HIV-seropositive subjects (P < 0.05) compared to that of controls. The sperm viability was significantly lower in HCV- and HBV-seropositive men than in controls (P < 0.001). The normal morphology was significantly reduced in HCV-seropositive and HBV-seropositive men (P < 0.05) with respect to that of controls (P < 0.05). The sperm concentration after sperm wash was significantly higher in controls than in HCV-, HIV-, HBV- and HIV-HCV-seropositive men (P < 0.001). We can conclude that HBV- and HCV-infected men have a significantly impaired sperm quality compared with that of controls. The reason for the better sperm quality in our series of HIV- and HCV-HIV-infected men is still under debate. Further investigations in a larger case series are warranted.

The PGC-1alpha-dependent pathway of mitochondrial biogenesis is upregulated in type I endometrial cancer.

PGC-1alpha-dependent pathway of mitochondrial biogenesis was investigated for the first time in type I endometrial cancer and in normal endometrium. In cancer endometrial tissue the citrate synthase activity, the mitochondrial DNA content and the TFAM level were found doubled compared to control endometrial tissue. Moreover, a 1.6- and 1.8-fold increase, respectively, of NRF-1 and PGG-1alpha expression was found. This study demonstrates, for the first time, that the increased mitochondrial biogenesis in type I endometrial cancer is associated to the upregulation of PGC-1alpha signalling pathway.

Modified radical hysterectomy versus extrafascial hysterectomy in the treatment of stage I endometrial cancer: results from the ILIADE randomized study.

BACKGROUND: Five percent to 20% of stage I endometrial cancer patients undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy develop vaginal and pelvic recurrences. Adjuvant radiotherapy can improve locoregional control but not survival. This randomized trial aimed to determine whether a modified radical (Piver-Rutledge class II) hysterectomy can improve survival and locoregional control compared to the standard extrafascial (Piver-Rutledge class I) hysterectomy. METHODS: Eligible patients (n = 520) with stage I endometrial cancer were randomized to class I or class II hysterectomy. Primary endpoint was overall survival. RESULTS: The median length of parametria and vagina removed were 15 and 5 vs. 20 mm and 15 mm for class I and class II hysterectomy, respectively (P > 0.001). Operating time and blood loss were statistically significantly higher for class II hysterectomy. At a median follow-up of 70 months, 51 patients had died. Five-year disease-free and overall survival were similar between arms (87.7 and 88.9% in the class I arm and 89.7 and 92.2% in the class II arm, respectively). The unadjusted hazard ratios for recurrence was 0.91 (95% confidence interval, 0.55-1.51, P = 0.72), and the hazard ratio for death was 0.77 (95% confidence interval, 0.44-1.33, P = 0.35). CONCLUSIONS: Class II hysterectomy did not improve locoregional control and survival compared to class I hysterectomy, but when an adequate vaginal cuff transection is not feasible with class I hysterectomy, a modified radical hysterectomy allows to obtain an optimal vaginal and pelvic control of disease with a minimal increase in surgical morbidity.

Cisplatin and vinorelbine chemotherapy in recurrent vulvar carcinoma.

PURPOSE: To evaluate the activity and toxicity of the combination of cisplatin and vinorelbine in patients with recurrent carcinoma of the vulva that has not been previously treated with chemotherapy. PATIENTS AND METHODS: Sixteen women with a median age of 65 years (range 43-79) with recurrent vulvar carcinoma were enrolled in the study. Nine patients had local recurrent disease (perineum, vagina and/or vulva), whereas 7 had disease in the groin; 9 patients had received prior radiotherapy. Cisplatin was administered intravenously on day 1 and vinorelbine was given on day 1 immediately after cisplatin and on day 8. RESULTS: A total of 68 cycles of chemotherapy were administered. Fifteen women were assessed for response. Objective responses were recorded in 6 patients (40%) - with 4 patients (27%) achieving a complete response and 2 (13%) achieving a partial response -, whereas 4 patients (27%) had stable disease and 5 had progressive disease. The median progression-free survival was 10 months (range 3-17), whereas the overall survival from the beginning of the chemotherapy was 19 months (range 1-30). Due to the small number of patients, no significant correlation with site of recurrence could be found. CONCLUSION: The combination of cisplatin and vinorelbine is a well-tolerated and active regimen in the treatment of patients with recurrent vulvar carcinoma.

Characterization of endometrial growth in proliferative and early luteal phase in IVF cycles.

Human endometrium has a definite role in implantation, although knowledge about its modifications in the course of IVF cycles is still limited. This study was performed to characterize endometrial growth throughout stimulation treatment in women undergoing IVF cycles, regardless of clinical outcomes. Endometrial growth was longitudinally evaluated by ultrasonography in the first induced ovarian stimulation cycle (717 patients). Acceleration and length of significant growth were used to assess the slope of the growth curve mathematically. Endometrial growth showed a parabolic trend and final thickness was significantly affected by age (P < 0.01). Endometria that tended to overgrowth had a more rapid and longer growth during the whole phase. A similar stimulation treatment was repeated within 6 months of the first one and a second evaluation was carried out to verify whether similar growth occurred. Similar growth was observed in 76% of the patients, with an absolute difference between the two cycles of <4 mm in 84% of cases. The endometrium seems to have an individual intrinsic potential that can be expressed regardless of the stimulation protocol. This supports the hypothesis that individual factors (intrinsic properties of the endometrium) significantly affect endometrial growth.

Apoptosis in normal ovaries of women with and without endometriosis.

The aim of this study was to evaluate the factors predisposing to implants of endometriotic lesions in normal ovarian cortexes of women with and without endometriosis by assessing the expression of pro-apoptotic and anti-apoptotic factors and follicular density. Ovarian biopsies were performed during laparoscopy in 18 patients with endometrioma and in 10 healthy women. Detection of apoptosis was performed with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay. p53 and BCL2 proteins were assessed by immunohistochemistry. Quantitative real-time polymerase chain reaction was performed to evaluate BAX , BAK , BCL2 , BCL-XL , survivin and beta-actin ( ACTB ) expression. The p53 protein was positive in a significantly higher number of secondary follicles, whereas the B-cell chronic lymphocytic leukaemia/lymphoma 2 (BCL2) protein was positive in all follicles in unaffected tissue of endometriotic women, compared with the controls. Overexpression of the BCL2 and survivin genes and a decreased BAX and BAK gene expression were observed in the endometriotic group although only the difference in survivin expression was significant (P = 0.016). The BCL2 / BAX ratio showed an increased value in the ovarian cortex in controls compared with endometriosis patients. In conclusion, the reduction of apoptosis in unaffected tissue in women with endometriosis suggests that they may be predisposed to develop endometriosis.

Follicular growth and oocyte maturation in GnRH agonist and antagonist protocols for in vitro fertilisation and embryo transfer.

BACKGROUND: The aim of this study was to evaluate the response to treatment in a group of patients undergoing IVF and randomised to receive GnRH-antagonist or the GnRH-agonist. The endpoints were the pattern of follicular growth, the maturity of the oocytes collected, the embryo quality and the pregnancy outcome. METHODS: A total of 136 patients undergoing IVF were included. Sixty-seven patients were allocated to the GnRH antagonist and 69 patients to the GnRH agonist. GnRH antagonist was administered when the leading follicle reached a diameter of 12-14 mm. GnRH agonist was administered in a long luteal protocol. RESULTS: The mean numbers of oocytes retrieved and mature oocytes were significantly higher in the agonist than in the antagonist group (p < 0.02 and p < 0.01, respectively). Embryo quality, implantation rate, clinical pregnancy rates, ongoing pregnancy rate and miscarriage rate were similar in both groups. CONCLUSIONS: Better follicular growth and oocyte maturation are achieved with GnRH agonist treatment. However, both regimens seem to have similar efficacy in terms of implantation and pregnancy rates. Further studies clarifying the effect of the GnRH antagonist on ovarian function are needed, as well as a clear definition of the best period of the follicular phase for the GnRH antagonist administration.