Short gonadotropin-releasing hormone agonist versus flexible antagonist versus clomiphene citrate regimens in poor responders undergoing in vitro fertilization: a randomized controlled trial.

OBJECTIVE: Poor responders represent a frustrating condition for couples undergoing IVF and clinicians, and their treatment remains disputed. To assess the efficacy and the most suitable protocol, we conducted a randomized controlled trial comparing three different protocols of ovarian stimulation in poor responder women: clomiphene citrate (CC) plus a high dose of gonadotropins and GnRH antagonist, flexible GnRH antagonist protocol and a short GnRH agonist protocol. PATIENTS AND METHODS: Between July 2014 and December 2015 we enrolled 250 poor responders in a previous IVF cycle at least 3 months before. We divided into three groups: group A, 68 women treated with clomiphene citrate and FSH plus antagonist; Group B, 71 patients treated with FSH plus antagonist; Group C, 75 patients treated with FSH plus GnRH agonist. RESULTS: The GnRH agonist protocol showed a significantly higher pregnancy rate (29.3% vs. 5.9% vs. 14.1% respectively) than the clomiphene and the GnRH antagonist protocol, number of mature oocytes collected, estradiol levels and endometrial thickness. The cost of medications for each baby born was lower for the GnRH agonist protocol than for the others; the implantation rate was significantly lower in the clomiphene group (4.8%) than in the GnRH antagonist group (9.3%) and the GnRH agonist groups (19.2%). No significant differences emerged for total FSH administered, days of stimulation, numbers of oocytes retrieved and embryos transferred. CONCLUSIONS: This study demonstrates that short GnRH agonist protocol should be the first choice in poor responders; instead, clomiphene citrate should be avoided due to its very low success rate and high costs.

Expression of E6/E7 HPV-DNA, HPV-mRNA and colposcopic features in management of CIN2/3 during pregnancy.

OBJECTIVE: The incidence of abnormal cervical cytology in pregnancy is similar to that reported for non-pregnant women. Furthermore, 1% of pregnant women annually screened for cervical cancer will be diagnosed with cervical intraepithelial neoplasia (CIN) of various degrees. For this reason, Pap smear should be performed in the first trimester of pregnancy. The persistence of HR-HPV infection is related to the development of CIN. However, the relationship between CIN and HR-HPV infection during pregnancy and postpartum can hardly be found. The aim of this work was to assess the proper management of abnormal cytology during and after pregnancy evaluating regression rate, persistence rate and risk of progression and the predictive role of HPV molecular tests. PATIENTS AND METHODS: Patients with abnormal cervical cytology were followed-up using colposcopy and colposcopy-directed biopsies every 12 weeks. Molecular tests were performed at the moment of the cytological diagnosis. Patients not treated in pregnancy were re-evaluated with cytology, colposcopy, biopsies, HPV-DNA test and HPV-mRNA test for a final diagnosis 8 weeks postpartum. Women with a persistent CIN 2-3 lesion at this follow-up check, underwent an excisional procedure by LEEP and then re-evaluated every 6 months for a year. RESULTS: HPV-DNA test showed a sensitivity of 90.5% and a negative predictive value of 96.4%. Specificity and positive predictive values were 67.9% and 43.2%, respectively. For HPV-mRNA test, a sensitivity of 76.2% and a NPV of 93.9% were found; specificity and PPV were 98.7% and 94.1% respectively. CONCLUSIONS: An observational management based on the use of molecular test and particularly HPV-mRNA test for its higher specificity, is a reasonable possibility in the follow-up of CIN2/3 lesions during pregnancy.

Human papilloma virus infection and cervical cytomorphological changing among intrauterine contraception users.

OBJECTIVE: The increased use of the intrauterine contraception (IUC) in female population and its probable relationship with cervical squamous intraepithelial lesions and cervical cancer make necessary clarify the possible interaction between the device and the pre-neoplastic lesions. PATIENTS AND METHODS: Seven hundred and eighty-nine patients users of IUC and 1491 patients ever users of IUC were followed every 6 months for 3 years. Each clinical control included Papanicolau test, colposcopy, HPV-DNA test and HPV-mRNA test. Also, in patients IUC users we analyzed the type of device, years of use and average age. RESULTS: Cytological sampling, histological examination, HPV-DNA test and HPV-mRNA test showed that there are not significantly differences between patients with or without IUC. CONCLUSIONS: None difference arose regarding persistence and progression between patients IUC users and IUC no users, for this reason, intrauterine contraception does not seem to be a co-causal factor in the possible development of cervical cancer.

Laparoscopic versus laparotomic surgery for adnexal masses: role in elderly.

BACKGROUND: The purpose of this study is to compare laparoscopy (LPS) and laparotomy (LPT), in terms of surgical outcomes, in elderly patients (>65 years) with adnexal masses. METHODS: We retrospectively reviewed a series of women older than 65 who had a diagnosis of adnexal masses. Then, all patients were divided into two different groups according to the type of surgery: 27 who underwent LPS (LPS group) and 24 who underwent LPT (LPT group). We took into consideration: age, comorbidity, histological diagnosis, surgery approach, and surgical outcome. Then, we calculated the percentages of all of these data and then χ (2) test and t-Student test were used to calculate the p value, to compare the two surgical techniques. A p value lower than 0.05 was considered to be statistically significant. RESULTS: At first, we evaluated the relation between the diagnosis and the surgery approach, and we obtained statistically significant results for serous cyst, adenocarcinoma serous/mucinous, and others, and the table highlights that some of the benign masses were mostly treated with LPS, while borderline and malignant masses were treated with LPT. Then, we evaluated the comorbidities of the patients, and we found that those cases had a significantly higher prevalence of cardiovascular disease and metabolic diseases. Finally, we compared the surgery outcome of LPS versus LPT surgeries for adnexal masses in elderly women, and there were statistically significant results for postoperative complications, number of patients who needed drainage, and number of days of hospitalization after surgery. CONCLUSIONS: Our results demonstrated that the patients who underwent LPS, compared to the patients who underwent LPT, have better outcomes in terms of postoperative complications (7.4 % with LPS and 37 % with LPT), number of patients who needed drainage (11.1 % with LPS and 62.5 % with LPT), and number of days of hospitalization after surgery, in term of mean (5 for LPS and 10.9 in term of LPT).

Quality of sex life in endometriosis patients with deep dyspareunia before and after laparoscopic treatment.

PURPOSE: The present work aims at showing how dyspareunia linked to endometriosis can affect the life of fertile age women and how surgical treatment of endometriosis can relieve painful symptoms and consequently improve sex and social life. METHODS: From a cohort of 320 women with a clinical and instrumental diagnosis of pelvic endometriosis, 67 patients were selected. These patients had deep dyspareunia that underwent laparoscopic surgical treatment. All the patients had filled out a pre- and post-surgery questionnaire. RESULTS: Six months after laparoscopic treatment, a significant reduction of dyspareunia was recorded, per VAS scores. A statistically significant improvement in sex life was observed between the pre- and post-surgical condition: in particular, an increased number of coituses and of non-difficult coituses, a higher number of patients who declared that pain did not negatively affect sexual pleasure and of patients achieving orgasm. CONCLUSIONS: The quality of the sex life in patients with endometriosis and dyspareunia showed significant improvement 6 months after laparoscopic treatment. In view of the diagnostic delay characterizing this disease and confirmed by our results, it is essential to involve a multidisciplinary team to assess all the signs and symptoms of endometriosis that may appear in a women of fertile age. This clinical approach is able to ensure a treatment that is as personalized as possible and an appropriate follow-up also with the objective of preserving reproductive performance.

Ovarian transposition in young women and fertility sparing.

OBJECTIVE: Ovarian transposition is a highly effective surgical procedure used to preserve ovarian function in premenopausal patients with cancers requiring postoperative or primary pelvic radiotherapy. Pelvic irradiation determines severe damage of ovarian DNA and iatrogenic ovarian failure with premature menopause, necessity of long-term hormone replacement therapy and infertility. MATERIALS AND METHODS: We conducted an extensive research of the literature in Medline between January 2000 and April 2015 using the key-words "ovarian transposition radiotherapy", "radiotherapy gonadal function", radiotherapy fertility sparing". The population included young women with normal ovarian function affected by cancers that required pelvic radiotherapy. We have examined 32 articles reporting on 1189 women undergoing ovarian transposition. Median age was 32.5 years, follow up was median 48 months. The procedure has been performed in patients less than 40 years of age. Surgery has been achieved by laparotomy or laparoscoy. We have analyzed effects of radiotherapy on ovarian function. RESULTS: The proportion of women treated by ovarian transposition preserved ovarian function was 70%. About 86% of patients did not develop ovarian cysts and in 98-99% of cases did not occur any metastatic disease. CONCLUSIONS: Ovarian transposition is associated with significant preservation of ovarian function and a low frequency of complications as cysts and metastasis. In 31% of cases the procedure can fail. Further studies are needed to evaluate the efficacy of ovarian transposition and the follow up. Ovarian transposition should be discussed at the time of cancer diagnosis in every premenopausal woman requiring pelvic radiotherapy.

Feasibility of office CO2 laser surgery in patients affected by benign pathologies and congenital malformations of female lower genital tract.

OBJECTIVE: Traditional surgery presents some disadvantages, such as the necessity for general anesthesia, hemorrhage, recurrence of pathology, and the possible onset of dyspareunia due to an excessive scarring. CO2 laser surgery might resolve these problems and might be employed in a wider range of clinical indications than usual. We examined the results of CO2 laser surgery in patients affected by benign pathologies and congenital malformations of the female lower genital tract. PATIENTS AND METHODS: In this observational study, we enrolled 49 women who underwent CO2 laser surgery for the following indications: Bartholin's gland cyst, imperforate hymen, vaginal septum, Nabothian cyst, and vaginal polyps. Feasibility, cost-effectiveness, complication rate, recurrence rate, short- and long-term outcomes were assessed. RESULTS: All procedures were carried out in a short operative time, without any intraoperative complications. Only 1 (2.0%) out of 49 patients required a hemostatic suture for bleeding. Postoperative period was uneventful in all patients, except 6 (12.2%) out of 49 patients who reported pain one day after surgery, successfully treated with paracetamol. Healing was rapid and excellent in all cases; no wound infection, scarring or stenosis were noticed. Preoperative symptoms reduced or disappeared in all cases. No recurrence was observed and no re-intervention was needed. CONCLUSIONS: CO2 laser surgery provides several advantages over traditional surgery, as its systematic use in treating pre-invasive, benign, and congenital pathologies of the female lower genital tract reduces patient discomfort, improves short- and long-term outcomes, and optimizes cost-effectiveness.

Diagnostic accuracy of sonohysterography vs hysteroscopy in benign uterine endocavitary findings.

OBJECTIVE: To compare diagnostic accuracy of sonohysterography vs hysteroscopy in patients with benign uterine endocavitary findings. PATIENTS AND METHODS: This retrospective study evaluated 202 patients submitted to sonohysterography after transvaginal ultrasound examination suspicious for uterine endocavitary findings. Cytological sample was taken and analyzed from the fluid used to distend the uterine cavity. Of 202 patients enrolled for this study, 86 patients underwent gynaecological surgery, of whom 77 were treated with operative hysteroscopy and 9 with other gynaecological surgical techniques. Statistical analysis was performed to evaluate diagnostic agreement between sonohysterography vs hysteroscopy and cytology vs histology. RESULTS: Diagnostic concordance between sonohysterography and hysteroscopy was significant (k value 0.87). The correlation between cytological and histological findings had a moderate level of concordance (k value 0.49). CONCLUSIONS: Sonohysterography provides a diagnostic accuracy as well as hysteroscopy, therefore, it could be considered an alternative procedure in the diagnosis of benign uterine endocavitary findings.

Adjuvant topical treatment with imiquimod 5% after excisional surgery for VIN 2/3.

OBJECTIVE: Vulvar intraepithelial neoplasia (VIN) is a premalignant lesion of the vulva. The incidence of VIN is increasing. The surgery is currently the gold standard therapy for VIN, but Imiquimod could be a completion to surgery. The aim of this study is to compare the overall complete response, the recurrence rate and the risk factors for recurrence among two groups of patients: women with high grade VIN underwent surgery and patients treated with surgery plus Imiquimod. PATIENTS AND METHODS: 80 patients with histologically diagnosed VIN 2/3 were enrolled in this prospective study. Our patients were divided into two groups: 40 women underwent surgery (A) and 40 patients were treated with surgery plus Imiquimod (B). All women had a 5-year follow-up. Recurrence rate and complete response were evaluated. The following patients' characteristics were analyzed: smoke, multifocal disease, multicentric disease, degree of the lesion. RESULTS: In the group A recurrence rate was 44.8%, in the group B it was 48.4%. In both groups the presence of multifocal lesions (p = 0.02) and VIN 3 (p = 0.006) before treatment was associated with a higher risk of recurrence. CONCLUSIONS: This study found that surgery remains the principal approach for VIN with regard to relapse and complete response since the treatment with Imiquimod associated with surgery didn't show a lower recurrence rate. Although the surgical treatments remain the best therapeutic option for VIN with regard to recurrence and overall complete response, the combined therapy seems to be an interesting modality, but further studies are needed.

Metergoline and bromocriptine in the management of tumoral and idiopathic hyperprolactinemia.

59 patients affected by amenorrhea or anovulation, 37 of whom also with galactorrhea, and with hyperprolactinemia of unknown origin (idiopathic hyperprolactinemia, 24 patients) or due to a pituitary microadenoma (tumoral hyperprolactinemia, 35 patients) were treated with metergoline (4-12 mg/day) or with bromocriptine (2.5 to 10 mg/day) for 90 days. The effectiveness of the two treatments was assessed on clinical grounds and by evaluating at monthly intervals serum progesterone levels, during the presumed luteal phase, and serum prolactin levels. The success rate with the two drugs was superimposable in terms of disappearance of galactorrhea and return of menses, normalization of prolactin levels and induction of ovulation. Also the number of pregnancies obtained (7 with metergoline, 9 with bromocriptine) was similar. With both drugs, the majority of patients responded to the treatment within the first month.

Treatment of hyperprolactinaemia with metergoline for periods up to 5 years: clinical and biological tolerability.

Forty patients with hyperprolactinaemia were treated with metergoline (8 to 12 mg/day) for periods up to 5 years. Analysis of the results of clinical and biological tolerability showed that treatment was generally well tolerated and although 28 patients complained of drug-related side-effects of various kinds, principally nausea, these were usually mild, present at the beginning of treatment and disappeared spontaneously in spite of continued metergoline administration over a prolonged period. No patient stopped treatment because of side-effects. Laboratory parameters also stayed within normal levels and there was no evidence of any alterations in the ECG. It is concluded, therefore, that metergoline is a well-tolerated as well as an effective ergolinic compound for use in those patients in whom prolonged treatment with a prolactin-lowering drug is considered necessary.