Influence of cryopreservation on perinatal outcome after blastocyst- vs cleavage-stage embryo transfer: systematic review and meta-analysis.

OBJECTIVE: To compare the perinatal outcomes of singleton pregnancies resulting from blastocyst- vs cleavage-stage embryo transfer and to assess whether they differ between fresh and frozen embryo transfer cycles. METHODS: A systematic review of the literature was carried out using the Scopus, MEDLINE and ISI Web of Science databases with no time restriction. We included only peer-reviewed articles involving humans, in which perinatal outcomes of singleton pregnancies after blastocyst-stage embryo transfer were compared with those after cleavage-stage embryo transfer. Primary outcomes were preterm birth before 37 weeks and low birth weight (< 2500 g). Secondary outcomes were very preterm birth before 32 weeks, very low birth weight (< 1500 g), small-for-gestational-age (SGA), large-for-gestational-age (LGA), perinatal mortality and congenital anomaly. A meta-analysis was performed using a random-effects model. Three subgroups were evaluated: fresh only, frozen only and fresh plus frozen embryo transfer cycles. RESULTS: From a total of 3928 articles identified, 14 were selected for qualitative/quantitative analysis. Significantly higher incidences of preterm birth < 37 weeks (11 studies, n = 106 629 participants; risk ratio (RR), 1.15 (95% CI, 1.05 - 1.25); P = 0.002) and very preterm birth < 32 weeks (seven studies, n = 103 742; RR, 1.16 (95% CI, 1.02-1.31); P = 0.03) were observed after blastocyst- than after cleavage-stage embryo transfer in fresh cycles. However, the risk of preterm and very preterm birth was similar after blastocyst- and cleavage-stage transfers in frozen and fresh plus frozen cycles. Overall effect size analysis revealed fewer SGA deliveries after blastocyst- compared with cleavage-stage transfer in fresh cycles but a similar number in frozen cycles. Conversely, more LGA deliveries were observed after blastocyst- compared with cleavage-stage transfer in frozen cycles (two studies, n = 39 044; RR, 1.18 (95% CI, 1.09-1.27); P < 0.0001) and no differences between the two groups in fresh cycles (four studies, n = 42 982; RR, 1.14 (95% CI, 0.97-1.35); P = 0.11). There were no differences with respect to low birth weight, very low birth weight or congenital anomalies between blastocyst- and cleavage-stage transfers irrespective of the cryopreservation method employed. Only one study reported a higher incidence of perinatal mortality after blastocyst- vs cleavage-stage embryo transfer in frozen cycles, while no differences were found in fresh cycles. CONCLUSIONS: Our results suggest that cryopreservation of embryos can influence outcome of pregnancy conceived following blastocyst- vs cleavage-stage embryo transfer in terms of preterm birth, very preterm birth, LGA, SGA and perinatal mortality. Caution should be exercised in interpreting these findings given the low level of evidence and wide heterogeneity of the studies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Human recombinant follicle stimulating hormone (rFSH) compared to urinary human menopausal gonadotropin (HMG) for ovarian stimulation in assisted reproduction: a literature review and cost evaluation.

BACKGROUND: Gonadotropins are protein hormones which are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function. There is still a lively debate on which type of gonadotropin medication should be used, either human menopausal gonadotropin or recombinant follicle-stimulating hormone. The objective of the study was to perform a systematic review of the recent literature to compare recombinant follicle-stimulating hormone to human menopausal gonadotropin with the aim to assess any differences in terms of efficacy and to provide a cost evaluation based on findings of this systematic review. METHODS: The review was conducted selecting prospective, randomized, controlled trials comparing the two gonadotropin medications from a literature search of several databases. The outcome measure used to evaluate efficacy was the number of oocytes retrieved per cycle. In addition, a cost evaluation was performed based on retrieved efficacy data. RESULTS: The number of oocytes retrieved appeared to be higher for human menopausal gonadotropin in only 2 studies while 10 out of 13 studies showed a higher mean number of oocytes retrieved per cycle for recombinant follicle-stimulating hormone. The results of the cost evaluation provided a similar cost per oocyte for both hormones. CONCLUSIONS: Recombinant follicle-stimulating hormone treatment resulted in a higher oocytes yield per cycle than human menopausal gonadotropin at similar cost per oocyte.

The combination of genetic variants of the FSHB and FSHR genes affects serum FSH in women of reproductive age.

STUDY QUESTION: What is the effect of FSHB-211G>T together with the FSHR 2039 A>G on serum FSH in women? SUMMARY ANSWER: Serum FSH levels are affected by the combination of genetic polymorphisms in FSHR and FSHB. WHAT IS KNOWN ALREADY: The relationship between SNPs of the FSHR gene and serum FSH has not been completely clarified. Genetic variants of the FSHB gene have been associated with variation in gene transcription and serum FSH levels in men. No data have been published on the effect of the FSHB-211G>T in women, alone or in combination with the FSHR 2039 A>G. STUDY DESIGN, SIZE, DURATION: This study was a prospective study including 193 healthy women of reproductive age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile and otherwise healthy eumenorrheic women (n = 193) with normal BMI and serum FSH levels were recruited for the study. In all women early follicular phase FSH and AMH were measured by commercial assays, and antral follicle count was measured by transvaginal ultrasound. Genomic DNA was purified from total peripheral blood and genotyping for the two SNPs was performed. MAIN RESULTS AND THE ROLE OF CHANCE: No significant gradients of increasing or decreasing Day 3 FSH across the FSHR 2039 (AA/AG/GG) and FSHB-211 (GG/GT/TT) genotypes, respectively, were observed. When women were stratified according to the FSHR 2039, and FSHB-211 genotypes a statistically significant reduction of d3 FSH was shown in the group of women with the FSHB-211 GT + TT/FSHR2039 AA genotype compared with the FSHB-211 GG/FSHR2039 GG genotype, hence confirming a possible additive effect of the different SNPs in FSHR and FSHB on regulating serum FSH. LIMITATIONS, REASONS FOR CAUTION: This finding requires an independent confirmation. However, it confirms the relationship between serum FSH and FSHB together with FSHR gene polymorphisms already reported in males. WIDER IMPLICATIONS OF THE FINDINGS: The knowledge of the FSHB/FSHR genotype combination is fundamental for the proper interpretation of serum FSH levels in women of reproductive age. STUDY FUNDING/COMPETING INTERESTS: Merck Serono supported the study in the form of a research grant for the laboratory session. None of the authors have any competing interest to declare.

A prospective, randomised, investigator-blind, controlled, clinical study on the clinical efficacy and tolerability of two highly purified hMG preparations administered subcutaneously in women undergoing IVF.

The aim of this multicentre, prospective, randomised, investigator blind, controlled clinical trial was to evaluate the clinical efficacy and tolerability of a highly purified human menopausal gonadotrophin (hMG) preparation (Merional-HG) when administered to patients undergoing controlled ovarian stimulation (COS) for in-vitro fertilisation (IVF) procedure enrolled in hospital departments. One hundred fifty-seven patients were randomised in two parallel groups: 78 started COS with Merional-HG and 79 with Menopur. Results of the study showed that both highly purified hMG preparations were equivalent in terms of number of oocytes retrieved (primary endpoint: 8.8 ± 3.9 versus 8.4 ± 3.8, p = 0.54). In the patients treated with Merional-HG, we observed a higher occurrence of mature oocytes (78.3% versus 71.4%, p = 0.005) and a reduced quantity of gonadotrophins administered per cycle (2.556 ± 636 IU versus 2.969 ± 855 IU, p < 0.001). Fertilisation, cleavage, implantation rates and the number of positive ß-human chorionic gonadotrophin (hCG; pregnancy) tests and the clinical pregnancy rate were comparable in the two groups. Both treatments were well tolerated. In conclusion, the results of this study support the efficacy and safety of Merional-HG administered subcutaneously for assisted reproduction techniques. Efficiency of Merional-HG appears to be higher due to reduced quantity of drug used and the higher yield of mature oocytes retrieved.

Vaginal lactoferrin in asymptomatic patients at low risk for pre-term labour for shortened cervix: cervical length and interleukin-6 changes.

A total of 3,324 singleton pregnant women were screened for pre-term delivery and 128 women were finally randomised and analysed for outcome showing borderline cervical length (25-29 mm) and elevated cervico-vaginal interleukin 6 levels. To verify if vaginal administration of lactoferrin might have an influence on these variables, two groups of 64 patients were formed. Study cases were submitted to lactoferrin for 21 days; controls received no treatment. An inverse relation was found between interleukin 6 levels and cervical length. On day 30 from the beginning of the treatment, study cases showed a decrease in interleukin 6 levels and an increase in cervical length. A greater number of women with regular uterine contractions and reduced cervical consistency before the 37th week of gestation were found in the controls. Our data show that lactoferrin could play a role in reducing the number of women at risk for pre-term birth for shortened cervical length and elevated interleukin 6 levels.

Who needs LH in ovarian stimulation?

LH plays a key role in the intermediate-late phases of folliculogenesis. Although ovarian stimulation is efficiently achieved in most cases by the administration of exogenous FSH alone, specific subgroups of women may benefit from LH activity supplementation during ovarian stimulation. Some authors have found improved outcome with LH activity supplementation in advanced reproductive age women. Experience suggests that in about 10-12% of young normogonadotrophic patients treated with a gonadotrophin-releasing hormone agonist (GnRH-a) long protocol plus recombinant FSH human (r-hFSH), a 'steady response' is observed. In this subgroup of women, a higher number of oocytes is retrieved when daily LH activity supplementation is given from stimulation day 8, if compared with the standard FSH dose increase. Another subgroup of patients who may benefit from LH activity supplementation are those at risk for poor ovarian response treated with GnRH antagonist. Recent data demonstrate that in these women, when GnRH is administered in a flexible protocol, the concomitant addition of recombinant human LH improves the number of mature oocytes retrieved, when compared with the standard GnRH-a flare-up protocol. Thus, well calibrated LH administration improves the ovarian outcome in patients >35 years, in those showing an initial abnormal ovarian response to r-hFSH monotherapy, and in 'low prognosis' women treated with GnRH antagonists.

Suboptimal response to GnRHa long protocol is associated with a common LH polymorphism.

The aim of this observational preliminary trial was to estimate the association between the most common polymorphism of LH (LH-ß variant: v-ßLH), with different profiles of ovarian response to recombinant human FSH (rhFSH). A total of 60 normogonadotrophic patients undergoing a gonadotrophin-releasing hormone analogue long down-regulation protocol followed by stimulation with recombinant human FSH (rhFSH) for IVF/intracytoplasmic sperm injection, and in whom at least five oocytes were retrieved were retrospectively included. On the basis of the total rhFSH consumption, patients were divided into three groups: Group A: 22 women requiring a cumulative dose of rhFSH >3500 IU; Group B: 15 patients requiring 2000-3500 IU; Group C (control): 23 women requiring <2000 IU. The presence of v-ßLH was evaluated using specific immunoassays. Peak oestradiol concentrations were significantly lower in Group A when compared with both groups B (P < 0.05) and C (P < 0.001). Group A had a significantly lower (P < 0.05) number of oocytes retrieved (7.3 ± 1.5, 11.7 ± 2.4 and 14.7 ± 4.1 in the three groups, respectively). Seven carriers (31.8%) of v-ßLH were found in Group A, whereas only one variant (6.7%) was observed in Group B; no variant was detected in Group C. These preliminary results suggest that v-ßLH is more frequent in women with ovarian resistance to rhFSH.

Suboptimal response to GnRHa long protocol is associated with a common LH polymorphism.

The aim of this observational preliminary trial was to estimate the association between the most common polymorphism of LH (LH-beta variant: v-betaLH), with different profiles of ovarian response to recombinant human FSH (rhFSH). A total of 60 normogonadotrophic patients undergoing a gonadotrophin-releasing hormone analogue long down-regulation protocol followed by stimulation with recombinant human FSH (rhFSH) for IVF/intracytoplasmic sperm injection, and in whom at least five oocytes were retrieved were retrospectively included. On the basis of the total rhFSH consumption, patients were divided into three groups: Group A: 22 women requiring a cumulative dose of rhFSH >3500 IU; Group B: 15 patients requiring 2000-3500 IU; Group C (control): 23 women requiring <2000 IU. The presence of v-betaLH was evaluated using specific immunoassays. Peak oestradiol concentrations were significantly lower in Group A when compared with both groups B (P < 0.05) and C (P < 0.001). Group A had a significantly lower (P < 0.05) number of oocytes retrieved (7.3 +/- 1.5, 11.7 +/- 2.4 and 14.7 +/- 4.1 in the three groups, respectively). Seven carriers (31.8%) of v-betaLH were found in Group A, whereas only one variant (6.7%) was observed in Group B; no variant was detected in Group C. These preliminary results suggest that v-betaLH is more frequent in women with ovarian resistance to rhFSH.

Surgery and out-patient data collection and reporting using Filemaker Pro.

OBJECTIVE: The application of an electronic database in clinical practice is used widespread in every field of medicine. The aim of the present study is to illustrate our experience to use a database software for documentation of two of our clinical activities, outpatient hysteroscopy and inpatient gynaecological surgery. PATIENTS AND METHODS: In 2004, we designed two databases, the first one to document surgical procedures in the operating theatre, the second to document outpatient hysteroscopy procedures using FileMaker v.8.5. The data entry interface contains free text fields for patient demographic data and the description of the surgical procedure, supplemented by drop-down lists for items such as clinical findings, procedures, instrumentation, technique, and complications. Copies were filed in the main hospital notes, sent to General Practitioners, and also given to our patients. RESULTS: Since August 2004, we have used our two databases to document 2766 gynaecological operations and 3777 outpatient hysteroscopies. All users particularly liked the dropdown lists as their use greatly reduced the time taken to enter each patient's data. The databases were regularly used to select patients for audit projects and research data collection for prospective studies. CONCLUSIONS: FileMaker is an user-friendly and easily configured software, extremely valuable in everyday clinical work.

The efficacy of modified luteal phase support with intramuscular progesterone in IVF/ICSI cycles: a retrospective observational study.

OBJECTIVE: The use of gonadotropin-releasing hormone agonist for ovulation triggering has become an intriguing topic in the last few years. As long as adequate luteal phase support is provided, it may be a valuable alternative to standard hCG triggering, associated with a significant reduction in OHSS incidence. Several luteal phase support options have been proposed, but few studies have addressed the issue of the appropriate route for progesterone administration to women triggered with GnRHa. The aim of the study was to evaluate the effect of GnRHa triggering on IVF/ICSI outcomes, using modified luteal phase support with intramuscular progesterone. PATIENTS AND METHODS: A retrospective study was carried out between January 2014 and December 2015, comparing the reproductive outcome in GnRHa triggered women given modified luteal phase support with intramuscular progesterone (Group A) with the outcome in women triggered with standard hCG (Group B) in IVF/ICSI cycles. RESULTS: 200 (Group A n = 100; Group B n = 100) consecutive normoresponder women were included. No differences with respect to Age, BMI, basal FSH, basal Estradiol and infertility diagnosis were observed between groups. Increased numbers of retrieved oocytes (8.1 ± 3.3 versus 6.8 ± 3.5, p = 0.009) and mature oocytes (5.8 ± 2.6 versus 5.1 ± 2.7, p = 0.03) were detected in Group A compared with Group B. Implantation, biochemical pregnancy and ongoing pregnancy rates were similar. CONCLUSIONS: Our findings confirmed that the GnRHa triggering strategy is associated with increased number of oocytes retrieved and of mature oocytes even in normoresponder women. Moreover, in these patients, the use of intramuscular progesterone during luteal phase support achieved satisfactory IVF outcomes.

High progesterone levels during the luteal phase related to the use of an aromatase inhibitor in breast cancer patients.

OBJECTIVE: To evaluate the hormonal profile in three breast cancer patients who underwent controlled ovarian stimulation in the presence of the aromatase inhibitor letrozole. PATIENTS AND METHODS: In IVF University referral center, a case series of three breast cancer patients who underwent controlled ovarian stimulation (COS) with recombinant FSH and letrozole were investigated. Ovulation was induced with hCG (case No. 1) or with GnRH agonist (case No. 2-3). The primary outcome of our study was the detection of progesterone levels in the luteal phase. RESULTS: Very high progesterone values (mean 186.6 ± 43.6 ng/mL) during the luteal phase were recorded in all three cases. CONCLUSIONS: High progesterone levels can be related to the use of letrozole independently of the most commonly used trigger regimen. Although progesterone has long been considered a protective factor against breast cancer, several studies have demonstrated that progesterone could expand a transformation-sensitive stem cell population in the mammary glands. The estrogen negative feedback effect on the hypothalamus-pituitary axis and the disruption of steroid biosynthesis and could represent an intriguing reason behind this phenomenon. Our results highlight the need to evaluate further the increase in progesterone levels in the luteal phase in women with breast cancer undergoing COS with letrozole.

Intra-follicular leptin concentration as a predictive factor for in vitro oocyte fertilization in assisted reproductive techniques.

BACKGROUND: Granulosa-cells are able to produce and store leptin, suggesting that this hormone is locally involved in the regulation of follicular growth. In this study, the role of follicular fluid (FF) leptin concentration in predicting oocyte fertilization and embryo quality was evaluated in 35 normogonadotrophic women undergoing controlled ovarian stimulation (COS) for assisted reproductive techniques. MATERIALS AND METHODS: Leptin concentration was measured in 47 consecutively collected FF in which a mature oocyte had been found during the ovum pick-up. Embryos deriving from fertilized oocytes were submitted to quality scoring systems. RESULTS: Mean leptin concentration was significantly higher in FF whose oocytes showed 2 pronuclei (no. 25) when compared with those with no evidence of fertilization (no. 22) at the 16-18 h check (26.0+/-6.1 vs 15.3+/-10.6 ng/ml, respectively, p<0.01). Follicular mean diameters were similar in the two groups (21.4+/-3.4 and 21.0+/-5.1 mm, respectively). Logistic regression analysis identified FF leptin levels as the best predictive parameter for oocyte fertilization (p<0.001). When receiving operating characteristics curve was employed, a FF leptin concentration of 20.25 ng/ml was the most reliable cut-off in predicting fertilization of oocytes. FF with leptin concentrations higher than this value (no. 27) had an oocyte fertilization rate of 85.7%. In contrast, FF levels < or =20.25 ng/ml (no. 20) were associated with a rate of 16.7% (p<0.05). No correlation emerged between FF leptin and the score attributed to 15 valuable embryos at the zygote stage (r=-0.01) and at 48 h after insemination (r=0.1). CONCLUSIONS: FF leptin levels are a better predictor of oocyte fertilization success rates than follicular diameter. These results underline the relevance of FF variables in developing methods for oocyte selection.

Acquired factor XII deficiency in a woman with recurrent pregnancy loss: working on a differential diagnosis in a single case.

BACKGROUND: Antiphospholipid syndrome (APS) has been often associated to RPL since 1980 and some reports in the Literature rarely described antibodies to factor XII in patients with APS. CASE HISTORY: We report the case history of 34-year-old caucasian women with recurrent fetal loss and persistent prolonged activated partial thromboplastin time. Haemostatic tests revealed persistent light decrease of clotting factor XII with normal values of IgG and IgM anticardiolipin antibodies and transient positivity for lupus anticoagulant (LA). Few reports in the Literature described antibodies to factor XII in patient with antiphospholipid syndrome (APS) and transient LA. So, once other causes of RPL were excluded, the patient was diagnosed an unusual form of APS associated to antibodies to factor XII, reduced factor XII plasma levels, transient LA and prolonged activated partial thromboplastin time. DISCUSSION: We suggest to consider also antibodies directed to clotting factors (e.g. factor XII in our case) as second step of thrombophilia screening in RPL, in particular if a persistent prolonged aPTT is present without an apparent cause.

Increased leptin levels in serum and peritoneal fluid of patients with pelvic endometriosis.

Pelvic endometriosis is an immune-related chronic inflammatory disease, characterized by ectopic implants of endometrium in the peritoneal cavity and associated with increased secretion of proinflammatory cytokines and neoangiogenesis. Leptin, the adipocyte-derived hormone, has been shown to have a role in food intake, basal metabolism, and reproductive function. Leptin levels are dynamically regulated, being elevated by inflammatory mediators and reduced by starvation. Leptin itself can influence the proinflammatory immune responses of CD4+ T lymphocytes, and reports have also shown this hormone to be an angiogenic factor in vitro and in vivo. We investigated whether leptin concentrations in serum and peritoneal fluid (PF) differed between 13 patients with different stages of endometriosis and 15 age- and body mass index-matched controls. We found a statistically significant (P < 0.05) increase in leptin levels in serum (30.3 +/- 14.8 ng/mL) and PF (35.9 +/- 17.4 ng/mL) of patients with endometriosis, compared with our control population (serum, 15.6 +/- 8.4; PF, 17.5 +/- 7.2 ng/mL). Regression equations, relating leptin to body mass index, were also significantly different in endometriosis patients, compared with controls. Higher levels of leptin were observed in the earlier stages of endometriosis than advanced-stage disease. These data suggest that the proinflammatory and neoangiogenic actions of leptin may contribute to the pathogenesis of endometriosis.

Carboplatin, cisplatin and paclitaxel in the treatment of patients with epithelial ovarian cancer.

BACKGROUND: Prognosis of advanced ovarian cancer is unsatisfactory. Chemotherapy can be intensified combining active drugs at their highest possible doses. PATIENTS AND METHODS: In this phase I/II trial, 77 untreated patients received escalating doses of paclitaxel (135, 155, 175, 195 and 215 mg/m2, infused over 3 hours) with carboplatin (AUC 3.6) and cisplatin (60 mg/m2). Nine, 16, 13, 8 and 3 patients were treated at the five levels, respectively. A further 28 patients were treated at the maximum tolerable dose (MTD). RESULTS: Dose-limiting toxicities (one WHO grade 3 constipation, one grade 2 prolonged peripheral neurotoxicity and one grade 3 cardiac toxicity) occurred at 215 mg/m2 in 3 out of 3 patients. MTD was reached at level 4 paclitaxel dose (195 mg/m2). Response was evaluated in 62 patients. A complete response was achieved in 23 patients (37.1%-95% CI 25.2-50.3), including 16 (25.8%) pathological and partial response in 28 (45.2%), for an overall response rate of 82.3% (95% exact CL: 70.5%-90.8%). The probability of response was affected by the degree of initial debulking (p = 0.002) and not by the paclitaxel dose. In patients with stage III-IV disease, median progression-free survival was 17 months (95% CI 14-25). After a median follow-up of 28 months, median survival had not been reached; 2-year estimated survival was 67%. CONCLUSION: Paclitaxel can be safely given at the dose of 195 mg/m2 in combination with carboplatin (AUC 3.6) and cisplatin (60 mg/m2). This combination is active and safe and could be considered in clinical settings requiring intensive short treatment.

Tubal patency after laparoscopic treatment of ectopic pregnancy.

OBJECTIVE: To evaluate operative course, tubal patency and reproductive performance after laparoscopic treatment of ectopic pregnancy in relation to initial human chorionic gonadotropin (hCG) values and to the kind of operation. DESIGN: Retrospective study. PATIENTS: Fourty-five patients affected by ectopic pregnancies: thirty-two treated with laparoscopic linear salpingotomy subvided into two groups depending on the hCG serum values < 10,000 mUl/ml (twenty patients: group 1) or > 10,000 mUl/ml (twelve patients Group 2), thirteen patients (Group 3) undergoing laparoscopic salpingectomy. Hysterosalpingographic examination was performed two or three months after surgery. MAIN OUTCOME MEASURES: Operative time, major surgical complications, tubal patency and pregnancy rate after surgery. RESULTS: Operative time was significantly (p < 0.05) lower in both group 1 and 3 (22.5 +/- 3.2 and 19.1 +/- 6.3, respectively) than in group 2 (39.4 +/- 5.6). Bilateral patent tubes were observed in eighteen cases of group 1 (90%) and eight cases of group 2 (60%). No statistically significant differences were found between the pregnancy rate of both group 1 (8/18) and 2 (3/8) and of group 3 (3/11). CONCLUSIONS: Reproductive outcome is similar in both conservative and destructive laparoscopic management of ectopic pregnancy: furthermore it shows a trend of improvement, not statistically significant, in conservative treatment.

Reproductive outcome after hysteroscopic metroplasty.

OBJECTIVE: To evaluate the reproductive outcome after hysteroscopic metroplasty. STUDY DESIGN: We analysed the reproductive outcome of 69 patients, with different degrees of septate uterus, undergoing hysteroscopic metroplasty in the outpatient infertility clinic of Naples 'Federico II' University. Of the 69 patients, 48 had a history of recurrent abortion while 21 had a primary infertility. In all cases the procedure was performed by means of the resectoscope. RESULTS: In 97.1% of the cases post-operative hysterosalpingogram or hysteroscopic examination showed a normal cavity with a little fundal notch. In two cases, second surgery was needed. Of the 48 patients affected by repeated abortion, 40 became pregnant after the metroplasty whereas, to date, in the infertile group only six out 21 (29.0%) conceived. We observed a total of 46 pregnancies with two sets of twins. Of these, 31 pregnancies (67.4%) were carried to term, five (10.8%) ended in preterm delivery, six (13%) ended in spontaneous abortion and four (8.6%) are in progress. Cervical cerclage was performed on 13 women. Only one (7.6%) woman with cervical cerclage had a preterm delivery, while the preterm delivery rate in women without cerclage was 12.1%. The modality of term pregnancy deliveries was cesarean section in 48% of the cases and vaginal delivery in the 52%. CONCLUSIONS: Our data analysis suggest that the correction of mullerian anomalies does not improve the pregnancy rate, but only the pregnancy outcome of the patients.

Screening for endometrial adenocarcinoma.

A careful evaluation of endometrial adenocarcinoma risk factors has allowed the AA. to suggest an integrated screening program, including cytology, hysteroscopy and guided biopsy. First results of this program are then described.

The adjuvant treatment of ovarian cancer: result of the pilot study of a new combination chemotherapeutic regimen (DAC).

Twenty-three previously untreated ovarian cancer patients were treated, from January 1986 to March 1987, with combination chemotherapy consisting of cisplatin, cyclophosphamide and cytarabine (DAC regimen). All patients had advanced disease, which included 18 stage III and 5 stage IV patients. Sixteen patients had serous, 6 undifferentiated and 1 mixed histotype. Surgery consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy and appendicectomy was performed in only 11/23 patients. Seventeen patients had bulky disease when the treatment was started. Four courses of chemotherapy were initially administered to all patients; second look laparotomy was performed in patients with no clinically measurable disease or with presumable entirely resectable tumor. Vomiting was the major side effect of chemotherapy: myelotoxicity was mild and in only one patient permanent renal damage occurred. A total of 14 objective clinical responses (73.7%) were observed, of which 9 were complete (47.4%). Six clinical complete remissions (37.5%) occurred in the group of patients with bulky disease. At second-look laparotomy six patients were found disease free (26%), 4 of whom originally had bulky disease (25%). Short-term DAC regimen seems to be a very effective treatment, with acceptable toxicity, in patients with ovarian cancer.

[Effects of danazol on the endometrium during peri-menopausal meno-metrorrhagia]. / Effetti del danazolo sull'endometrio nella menometrorragia perimenopausale.

Perimenopausal abnormal bleeding is one of the most common gynecological problems. We have assessed the effectiveness of danazol 200 mg daily for 3 months in 42 patients with perimenopausal abnormal bleeding without any previous treatment and in 23 patients previously treated with norethisterone or medroxyprogesterone acetate but with a recurrence of bleeding 2 months after the end of the treatment. In the overall population treated by danazol at the end of treatment we had: bleeding normalized in 88.2% and hysteroscopic patterns, showing regression of hyperplasia in 95% of cases. The endometrial effects were maintained 2 months after the end of treatment with an increase of the hyperplastic pictures at 4 (26%) and up to 12 months (60%). We had amenorrhea in 10% of patients at the end of treatment and in 2 cases only treatment was discontinued for severe side effects. The comparison of these better results with those obtained by progesterone agents and with those of a preliminary experience with GnRH agonists had led us to consider the importance of an additional endometrial effects exerted by danazol. Particularly the immunosuppressive properties of this drug, as we have shown in "in vitro" conditions, can determine a decreased secretion of growth factors by local immune cells which in turn can further explain the endometrial antiproliferative action of this drug.