Benign descriptors and ADNEX in two-step strategy to estimate risk of malignancy in ovarian tumors: retrospective validation in IOTA5 multicenter cohort.

OBJECTIVE: Previous work has suggested that the ultrasound-based benign simple descriptors (BDs) can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. This study aimed to validate a modified version of the BDs and to validate a two-step strategy to estimate the risk of malignancy, in which the modified BDs are followed by the Assessment of Different NEoplasias in the adneXa (ADNEX) model if modified BDs do not apply. METHODS: This was a retrospective analysis using data from the 2-year interim analysis of the International Ovarian Tumor Analysis (IOTA) Phase-5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during 1 year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria. RESULTS: A total of 8519 patients were recruited at 36 centers between 2012 and 2015. We excluded patients who were already in follow-up at recruitment and all patients from 19 centers that did not fulfil our criteria for good-quality surgical and follow-up data, leaving 4905 patients across 17 centers for statistical analysis. Overall, 3441 (70%) tumors were benign, 978 (20%) malignant and 486 (10%) uncertain. The modified BDs were applicable in 1798/4905 (37%) tumors, of which 1786 (99.3%) were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver-operating-characteristics curve (AUC) of 0.94 (95% CI, 0.92-0.96). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two-step strategy without CA125 of 0.93 (95% CI, 0.91-0.95). CONCLUSION: A large proportion of adnexal masses can be classified as benign by the modified BDs. For the remaining masses, the ADNEX model can be used to estimate the risk of malignancy. This two-step strategy is convenient for clinical use. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Assessing and validating housekeeping genes in normal, cancerous, and polycystic human ovaries.

PURPOSE: Housekeeping genes (HKGs), reference or endogenous control genes, are vital to normalize mRNA levels between different samples. Since using inappropriate HKGs can lead to unreliable results, selecting the proper ones is critical for gene expression studies. To this end, normal human ovaries, as well as those from patients diagnosed with ovarian endometrioid adenocarcinoma (OEA), ovarian mucinous adenocarcinoma (OMA), ovarian serous papillary carcinoma (OSPC), and polycystic ovary syndrome (PCOS), were used to identify the most suitable housekeeping genes. METHODS: RNA was isolated from 5 normal human ovaries (52-79 years of age), 9 cancerous ovaries (3 OEA, 3 OMA, 3 OSPC; 49-75 years of age), and 4 PCOS ovaries (18-35 years of age) in women undergoing hysterectomy. cDNA was synthesized using a whole transcriptome kit, and quantitative real-time PCR was performed using TaqMan array 96-well plates containing 32 human endogenous controls in triplicate. RESULTS: Among 32 HKGs studied, RPS17, RPL37A, PPIA, 18srRNA, B2M, RPLP0, RPLP30, HPRT1, POP4, CDKN1B, and ELF1 were selected as the best reference genes. CONCLUSIONS: This study confirms recent investigations demonstrating that conventional HKGs, such as GAPDH and beta-actin, are not suitable reference genes for specific pathological conditions, emphasizing the importance of determining the best HKGs on a case-by-case basis and according to tissue type. Our results have identified reliable HKGs for studies of normal human ovaries and those affected by OEA, OMA, OSPC, or PCOS, as well as combined studies of control subjects vs. each cancer or PCOS group.

Pituitary block with gonadotrophin-releasing hormone antagonist during intrauterine insemination cycles: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Several randomised controlled trials (RCTs) have investigated the usefulness of pituitary block with gonadotrophin-releasing hormone (GnRH) antagonists during intrauterine insemination (IUI) cycles, with conflicting results. OBJECTIVE: The aim of the present systematic review and meta-analysis of RCTs was to evaluate the effectiveness of GnRH antagonist administration as an intervention to improve the success of IUI cycles. SEARCH STRATEGY: Electronic databases (MEDLINE, Scopus, EMBASE, Sciencedirect) and clinical registers were searched from their inception until October 2017. SELECTION CRITERIA: Randomised controlled trials of infertile women undergoing one or more IUI stimulated cycles with GnRH antagonists compared with a control group. DATA COLLECTION AND ANALYSIS: The primary outcomes were ongoing pregnancy/live birth rate (OPR/LBR) and clinical pregnancy rate (CPR). Pooled results were expressed as odds ratio (OR) or mean differences with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. The body of evidence was rated using GRADE methodology. Publication bias was assessed with funnel plot, Begg's and Egger's tests. MAIN RESULTS: Fifteen RCTs were included (3253 IUI cycles, 2345 participants). No differences in OPR/LBR (OR 1.14, 95% CI 0.82-1.57, P = 0.44) and CPR (OR 1.28, 95% CI 0.97-1.69, P = 0.08) were found. Sensitivity and subgroup analyses did not provide statistical changes in pooled results. The body of evidence was rated as low (GRADE 2/4). No publication bias was detected. CONCLUSION: Pituitary block with GnRH antagonists does not improve OPR/LBR and CPR in women undergoing IUI cycles. TWEETABLE ABSTRACT: Pituitary block with GnRH antagonists does not improve the success of IUI cycles.

Correction to: Contribution of cryopreservation to the cumulative live birth rate: a large multicentric cycle-based data analysis from the Italian National Registry.

The original article unfortunately contained a mistake. The names of the collaborators were captured as authors of the article.

Contribution of cryopreservation to the cumulative live birth rate: a large multicentric cycle-based data analysis from the Italian National Registry.

PURPOSE: To estimate the contribution of cryopreservation to the cumulative live birth rate (CLBR) after law modification in Italy in the era of vitrification and freeze-all. METHODS: The Italian National Registry performed a cycle-based data collection. Nine Italian IVF clinics were involved incorporating a total of 10,260 fresh cycles performed between January 2015 and April 2016 resulting in 9273 oocyte retrievals and 3266 subsequent warming cycles from the same oocyte retrievals performed up to December 2016. Mean female age was 37 ± 4.3 years. Primary outcome measure was CLBR per oocyte retrieval. Confounding factors were tested in multivariate regression analysis, and the relative impact of cryopreservation to the CLBR in different patient categories was calculated. RESULTS: CLBR per oocyte retrieval was 32.6%, 26.5%, 18.7%, 13.0%, and 5.5% for women younger than 36, aged 36-39, 40-41, and older than 41 years, respectively. The total relative contribution of oocyte/embryo cryopreservation was 40.6% (95% CI 38.41-42.75). An association between maternal age, number of oocytes retrieved, fertilization rate, cryopreservation, and cumulative live birth was shown. When adjusted for confounders, a 2.3-fold increase was observed in the chance of live birth when cryopreservation was performed (OR 2.3; 95% CI 1.99-2.56). In high responder patients (> 15 oocytes retrieved) where freeze-all was applied in 67.6% of cycles to avoid the risk of hyper stimulation syndrome, the relative contribution of vitrification to the CLBR was 80.6%. CONCLUSIONS: Cryopreservation is essential in IVF and should always be available to patients to optimize success rates. Multicentric, cycle-based data analyses are crucial to provide infertile couples, clinicians, and regulatory bodies with accurate information on IVF effectiveness including fresh and cryopreserved cycles.

Testicular sperm extraction after laparoscopic orchiectomy for bilateral postpubertal intra-abdominal cryptorchidism: What chance of sperm retrieval?

Infertility occurs in up to 54% of men with bilateral undescended testes. Orchiectomy is considered the best therapeutic approach, especially when cryptorchidism is diagnosed in adulthood, due to a high risk of malignancy. A 33-year-old man was referred with a clinical presentation of empty scrotum and an ultrasonography and magnetic resonance imaging evaluation of intra-abdominal bilateral cryptorchidism. Follicle-stimulating hormone was 23.20 IU/L, luteinising hormone was 14.10 IU/L, total testosterone was 12.1 nmol/L, and 17-beta-oestradiol was 0.16 nmol/L. Semen analysis showed absolute azoospermia. Tumour marker levels were in the normal range. Testicular volume was 4.0 ml for right testis and 4.6 ml for left testis. The patient underwent a laparoscopy bilateral orchiectomy and subsequently a testicular sperm extraction (TESE), in the purpose to finding mature spermatozoa. The biological examination revealed the presence of immature sperm cells, not efficient for a cryopreservation. The histologic analyses show a pattern of Sertoli cell-only syndrome and maturation arrest. TESE might be a good option for patients with absolute azoospermia and cryptorchidism, especially if bilateral. The procedure, performed after orchiectomy, is safe and does not have any impact on patient's health, although it is important to clarify the very low potential of sperm recovery.

Are hormone measurements and ultrasounds really predictors of sperm retrieval in testicular sperm extraction? A case report and literature review.

Azoospermia can be diagnosed in about 10%-15% of the infertile male population. To overcome the problem of failure to produce spermatozoa in the ejaculate in patients with nonobstructive azoospermia (NOA), testicular sperm extraction (TESE) may be performed to find the focal area of spermatogenesis. A 47-year-old man with NOA presented for treatment of secondary couple infertility. The patient underwent a first TESE 7 years earlier with cryopreservation, and an intracytoplasmic sperm injection-embryo transfer ended in a term pregnancy. He reported a history of repeated testicular traumas. At the present time, a complete medical workup was carried out, including clinical history, general and genital physical examination, scrotal and transrectal ultrasounds. Hormone measurements showed follicle-stimulating hormone level of 42.7 IU/L, luteinising hormone of 11.4 IU/L, total testosterone of 2.6 ng/ml and right and left testicular volume, respectively, of 4 and 3.9 ml. He underwent a second TESE, with successful sperm retrieval and cryopreservation. The histological pattern was hypospermatogenesis. In cases of extreme testicular impairment, although in the presence of very high follicle-stimulating hormone value and small testicular volume, estimating poor sperm recovery potential, the integration of clinical and anamnestic data, could help the surgeon to practise the more appropriate method of treatment.

Clinical and ultrasound characteristics of surgically removed adnexal lesions with largest diameter ≤ 2.5 cm: a pictorial essay.

OBJECTIVES: To describe the ultrasound characteristics, indications for surgery and histological diagnoses of surgically removed adnexal masses with a largest diameter of ≤ 2.5 cm (very small tumors), to estimate the sensitivity and specificity of diagnosis of malignancy by subjective assessment of ultrasound images of very small tumors and to present a collection of ultrasound images of surgically removed very small tumors, with emphasis on those causing diagnostic difficulty. METHODS: Information on surgically removed adnexal tumors with a largest diameter of ≤ 2.5 cm was retrieved from the ultrasound databases of seven participating centers. The ultrasound images were described using the International Ovarian Tumor Analysis terminology. The original diagnosis, based on subjective assessment of the ultrasound images by the ultrasound examiner, was used to calculate the sensitivity and specificity of diagnosis of malignancy. RESULTS: Of the 129 identified adnexal masses with largest diameter ≤ 2.5 cm, 104 (81%) were benign, 15 (12%) borderline malignant and 10 (8%) invasive tumors. The main indication for performing surgery was suspicion of malignancy in 22% (23/104) of the benign tumors and in all 25 malignant tumors. None of the malignant tumors was a unilocular cyst (vs 50% of the benign tumors), all malignancies contained solid components (vs 43% of the benign tumors), 80% of the borderline tumors had papillary projections (vs 21% of the benign tumors and 20% of the invasive malignancies) and all invasive tumors and 80% of the borderline tumors were vascularized on color/power Doppler examination (vs 44% of the benign tumors). The ovarian crescent sign was present in 85% of the benign tumors, 80% of the borderline tumors and 50% of the invasive malignancies. The sensitivity of diagnosis of malignancy by subjective assessment of ultrasound images was 100% (25/25) and the specificity was 86% (89/104). Excluding unilocular cysts, the specificity was 71% (37/52). Analysis of images illustrated the difficulty in distinguishing benign from borderline very small cysts with papillations and benign from malignant very small well vascularized (color score 3 or 4) solid adnexal tumors. CONCLUSIONS: Very small malignant tumors manifest generally accepted ultrasound signs of malignancy. Small unilocular cysts are usually benign, while small non-unilocular masses, particularly ones with solid components, incur a risk of malignancy and pose a clinical dilemma. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Gynaecological endoscopic evaluation of 4% icodextrin solution: a European, multicentre, double-blind, randomized study of the efficacy and safety in the reduction of de novo adhesions after laparoscopic gynaecological surgery.

BACKGROUND: Gynaecological laparoscopic surgery outcomes can be compromised by the formation of de novo adhesions. This randomized, double-blind study was designed to assess the efficacy and safety of 4% icodextrin solution (Adept(®)) in the reduction of de novo adhesion incidence compared to lactated Ringer's solution (LRS). METHODS: Patients undergoing laparoscopic surgery for removal of myomas or endometriotic cysts were treated with randomized solution as an intra-operative irrigant and 1l post-operative instillate. De novo adhesion incidence (number of sites with adhesions), severity and extent were independently scored at a second-look procedure and the efficacy of the two solutions compared. The effect of surgical covariates on adhesion formation was also investigated. Initial exploratory analysis of individual anatomical sites of clinical importance was progressed. RESULTS Of 498 patients randomized, 330 were evaluable (160 LRS--75% myomectomy/25% endometriotic cysts; 170 Adept--79% myomectomy/21% endometriotic cysts). At study completion, 76.2% LRS and 77.6% Adept had ≥ 1 de novo adhesion. The mean (SD) number of de novo adhesions was 2.58 (2.11) for Adept and 2.58 (2.38) for LRS. The treatment effect difference was not significant (P = 0.909). Assessment of surgical covariates identified significant influences on the mean number of de novo adhesions regardless of treatment, including surgery duration (P = 0.048), blood loss in myomectomy patients (P = 0.019), length of uterine incision in myomectomy patients (P < 0.001) and number of suture knots (P < 0.001). There were 15 adverse events considered treatment-related in the LRS patients (7.2%) and 18 in the Adept group (8.3%). Of 17 reported serious adverse events (9 LRS; 8 Adept) none were considered treatment-related. CONCLUSIONS: The study confirmed the safety of Adept in laparoscopic surgery. The proportion of patients with de novo adhesion formation was considerably higher than previous literature suggested. Overall there was no evidence of a clinical effect but various surgical covariates including surgery duration, blood loss, number and size of incisions, suturing and number of knots were found to influence de novo adhesion formation. The study provides direction for future research into adhesion reduction strategies in site specific surgery.

Influence of male human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection on the reproductive outcomes in serodiscordant couples: a case-control study.

BACKGROUND: Nowadays, serodiscordant couples (SDCs) with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)-infected men have the chance to conceive safely, giving birth with a minimum risk of cross-infection. OBJECTIVE: To assess the impact of male HIV and HCV infection on the assisted reproductive technologies (ART) outcomes in SDCs, with HIV or HCV seropositive men and negative partners. MATERIALS AND METHODS: Of 153 couples: 24 in Group 1 (HIV-seropositive men), 60 in Group 2 (HCV-seropositive men) and 69 in Group 3 (controls). Sperm-washing procedure was performed using a three-step system. Fresh ICSI cycles were carried out in HIV SDCs, HCV SDCs and controls. Seminal parameters, fertilization rate (FR), cleavage rate (CR), pregnancy rate per cycle (PR/C), miscarriage rate, implantation rate (IR) and live birth rate were evaluated. RESULTS: All the seropositive men have undetectable viral loads at the time of insemination, and both partners were free from co-morbid infections. The median number of embryos transferred was 2.0 (IQR 1.0-3.0), with no differences among groups. FR was significantly reduced in HIV and HCV SDCs compared to the controls (66%, 61% and 75%, respectively; p < 0.01). CR was similar between groups (p = 0.3). IR was 12.1%, 11.1% and 14.1%, respectively, in the three groups (p = 0.30). PR/C was 21.7%, 17.6% and 20.2% in HIV, HCV and controls, respectively. Live birth rate per cycle was 17.4%, 15.7% and 15.9%, respectively. There were no significant differences in clinical pregnancies per cycle, as well as miscarriages and live births (p = 0.30; 0.30; 0.60, respectively). CONCLUSIONS: The sperm-washing technique with ICSI may generate a promising way to improve pregnancy outcomes and to reduce the risk of viral transmission in these couples. In this setting, we can correctly counsel HIV- and HCV-infected men of SDCs with regard to the likelihood of father their own biological child.

Short-term FSH treatment and sperm maturation: a prospective study in idiopathic infertile men.

The standard FSH treatment is based on a 3 months period, after which both quantitative/qualitative improvement of sperm parameters and increased pregnancy rate were reported. In this prospective clinical trial, for the first time, we studied (i) Sperm hyaluronic acid binding capacity after highly purified FSH (hpFSH) treatment; (ii) the effect after short-term and standard treatment on this functional parameter. As secondary objective, we analyzed three SNPs on FSHß and FSHR genes to define their potential predictive value for responsiveness. From a total of 210 consecutive patients, 40 oligo- and/or astheno- and/or teratozoospermic patients fulfilled the inclusion criteria. Treatment consisted in hpFSH 75 IU/L every other day for 3 months. To avoid potential biases derived from the lack of placebo, we analyzed each patient after 4-6 months of 'wash-out' period. After FSH treatment, we observed a statistically significant (p < 0.001) improvement of the percentage of hyaluronic acid bound spermatozoa from basal to T1 (after 1 month) and to T3 (after 3 months). Importantly, these values returned to near-baseline value after the wash-out. The same results were detected for total motile sperm count after 3 months with return to baseline after wash-out. Forty-two percent of patients responded to the therapy with increasing hyaluronic acid binding capacity above the double of the Intraindividual Variation (IV) while 24% of patients reached above the normal Sperm-Hyaluronan Binding Assay (HBA) value. Further increase in 'responders' was observed at T3. The responsiveness to treatment resulted independent from FSHR/FSHß polymorphisms. The significant positive effect on sperm maturity after 1 month opens novel therapeutic perspectives. In view of both the high cost and the relative invasiveness of treatment, the short protocol (1 month) could represent a viable FSH treatment option prior Assisted Reproductive Techniques since FSH, by acting on sperm maturation, increases the proportion of functionally competent cells.

Diagnosis and treatment of endometriosis. A review.

The correct approach for endometriosis management is still unclear. This review explores recent data concerning diagnosis and treatment of endometriosis, trying to define guidelines for the most appropriate diagnostic approach and therapeutic regimen. At present, laparoscopy is still considered the gold standard in endometriosis diagnosis. The risks and the diagnostic limitations of laparoscopy and the inaccuracy of clinical examination justify the considerable efforts made to improve the diagnosis with imaging techniques. The therapeutic approach is still far from being defined as causal and focuses on management of clinical symptoms of the disease rather than on the disease itself. A first-line medical therapy should be tried in patients with pelvic pain not asking for a pregnancy. Surgical treatment is considered the best treatment for women with pain and or pelvic mass who wish to become pregnant in a short time. For infertile patients, medical therapy has a limited role. The 2 treatment options include surgery or in vitro fertilization (IVF). According to our results, it seems that correct management of infertile women with endometriosis is a combination of surgery and IVF in women who did not obtain post-surgery pregnancy spontaneously.

Clinical, ethical, and medical legal considerations on emergency contraception.

PURPOSE OF INVESTIGATION: To evaluate how many women required the so-called "emergency contraception" at our outpatient service and what the actual role is of this kind of pharmacological administration in interfering with ovulation and pregnancy, paying particular attention to the ethical and medico-legal aspects of this subject. METHODS: During the period from 1 December 1998 to 30 November 2003, emergency contraception was prescribed to a total of 1,160 women. With regard to the contraceptives used, in most cases (1,132, 97.6%) a combined oral estrogen-progestogen pill (ethinyloestradiol 0.05 mg plus levonorgestrel 0.25 mg) was prescribed; in some cases (20 patients, 1.8%) danazol (400 mg), in four women (0.3%) a progestin-only pill (levonorgestrel 0.75 mg), and in four other women (0.3%) an intrauterine device. RESULTS: It does not come out that there were any pregnancies in our study patients since none of them, who were told to come back for follow-up, were seen at our termination of pregnancy service or delivery room. CONCLUSION: The "Yuzpe regimen" of a combined oral estrogen-progestogen pill has been the most commonly used method for emergency contraception. A new method recently proposed, a progestin-only pill with levonorgestrel 0.75 mg, is having better results than the previous one, with a lower incidence of side-effects and higher efficacy. Moreover, the treatment with this method does not interfere in case of a pregnancy already being carried and cannot interrupt it.

Fetal and neonatal ovarian cysts: what's their real meaning?

PURPOSE OF INVESTIGATION: The management of fetal ovarian cysts is still controversial despite the improvement in prenatal diagnosis with ultrasonography. Some studies suggest an aggressive management, while others opt for a conservative one. The prognosis of the majority of congenital ovarian cysts is good since they have a benign origin. Sometimes, however, complications such as torsion or rupture can occur which often require surgical intervention after delivery. In this paper we report our experience and a brief review of the literature. METHODS: The authors report on 32 pregnant women in whom ultrasonography revealed the presence of an echo-rare or echo-free area in the fetal abdomen suggestive of an ovarian cyst. All women were followed-up during pregnancy with serial ultrasound examinations. Postnatal ultrasound controls confirmed the prenatal diagnosis in all cases. The diameters of the cysts ranged from 2.7 to 7.5 cm. RESULTS: In the 16 cases (50%) in which the cyst diameter was below 4 cm, periodic ultrasound examinations revealed a tendency towards spontaneous regression of the cysts. In the other 16 cases (50%) in which the cyst diameter exceeded 4 cm, cystectomy was necessary due to subsequent complications (torsion in 6 cases, 37.5%, and intracystic hemorrhage in the other 10, 62.5%). CONCLUSION: The most appropriate clinical approach in the management of benign feto-neonatal ovarian cysts is to adopt a wait-and-see policy, assessing the course of the condition by means of periodic ultrasound monitoring. Only when tumefactions measure more than 4 cm in diameter with attendant complications is surgical therapy indicated. Without complications, however, aspiration of the cystic contents is possible even in ovarian cysts exceeding 4 cm in diameter.

Role of infection in in vitro fertilization treatment.

With the increasing demand for assisted reproductive techniques (ARTs), it is important to consider how to manage infection. Three main positive factors that contribute to successful in vitro fertilization (IVF) cycles are maternal age, the ovarian hyperstimulation protocol used, and the number and quality of transferred embryos. Negative factors include contamination and infection. This paper describes the issues relating to infection during IVF and proposes guidelines to control infection and to increase laboratory safety.

Pressure lavage under ultrasound guidance: a new approach for outpatient treatment of intrauterine adhesions.

OBJECTIVE: To present pressure lavage under ultrasound guidance (PLUG) as a new therapeutic procedure for selected cases of intrauterine adhesions (IUA). DESIGN: An open clinical investigation with no control group. SETTING: Teaching hospital. PATIENT(S): Seven consecutive patients referred to our department for secondary amenorrhea due to IUA. INTERVENTION(S): A newly developed technique based on sonohysterography was used to monitor the effects of intrauterine injections of saline solution on the continuous accumulation of saline in the uterine cavity for the mechanical disruption of IUA. MAIN OUTCOME MEASURE(S): Lysis of intrauterine adhesions, restoration of menses, and increased pregnancy rate in infertile patients. RESULT(S): Five patients with mild IUA obtained satisfactory lysis of adhesions by the use of the PLUG technique. A second-look hysteroscopy after 1 month showed that filmy adhesions persisted in two patients with moderate IUA. These adhesions were removed successfully during hysteroscopy. Restoration of menses was obtained and has continued in all patients. Two of the three infertile patients became pregnant. CONCLUSION(S): This technique is safe and ideal as an in-office procedure. PLUG allows complete lysis in mild IUA cases, and the need for therapeutic, and possibly follow-up hysteroscopy, can be avoided. In moderate IUA cases, the procedure may represent a useful initial step in reducing the need for operative hysteroscopy.

The use of intravenous methotrexate in the treatment of ectopic pregnancy.

Between January 1996 and December 2001, at the Department of Gynecology, Perinatology and Human Reproduction of the University of Florence, 49 ectopic pregnancies were submitted to medical treatment. The treatment schedule consisted of the administration of 100 mg of intravenous methotrexate (MTX). The patients included in this study fulfilled the following requisites: gestational period <8 weeks; diameter of the ectopic gestational sac <4 cm; serum level of human chorionic beta-gonadotropin (beta-hCG) <5000 IU/ml; absence of clinical and ultrasound signs of tube rupture with initial hemoperitoneum; hematochemical tests compatible with chemotherapic treatment. All patients were followed with a dosage of serum beta-hCG repeated every 2-3 days after chemotherapy and with an ultrasound every 3-4 days. In case of documented success of treatment the patient was hospitalized for no more than 3 days after administration of the drug. In 1 case therapy took place in a day-hospital regimen. Medical treatment was effective in 35 patients out of 49 (71.4%) and led to negative beta-hCG in a median time of 11 days, with a range between 2 and 48 days. In the 14 non-responsive cases (28.6%), after a mean time of 6 days we proceeded to a traditional surgical approach or laparoscopy. In none of the cases did we find significant pharmacological toxicity, while in 9 patients (18.3%), severe painful symptoms appeared immediately after treatment, but resolved within 24 hours. Our results are interesting and in agreement with other experiences found in the literature. In our opinion, the advisability of a second administration in case of slow response, the comparison with an analogous intramuscular treatment, a more precise definition of the eligibility criteria, long-term follow-up of the patients, especially in case of subsequent pregnancies should all be further considered.

Hormonal patterns, steroid receptors and morphological pictures of endometrium in hyperstimulated IVF cycles.

OBJECTIVE: The purpose of this contribution is to investigate the pathophysiology of the abnormal endometrial development in hyperstimulated IVF cycles. STUDY DESIGN: In 12 IVF-patients who did not have embryo transfer because of failure of oocyte fertilization, serum values of 17 beta-estradiol, progesterone, FSH, LH, total and free testosterone, and androstenedione were measured on the pick-up day and were evaluated with respect to the values normally expressed in the day of ovulation; in the endometrial specimens collected 2 days later, at the time of embryo replacement, estrogen and progesterone receptors were immunohistochemically determined and dating by the Noyes method was performed. RESULTS: 17 beta-Estradiol values are constantly higher, and progesterone levels are, only in four cases, higher than expected for the day of ovulation in a natural cycle. These hormonal patterns can only partially explain the pattern of steroid receptors: progesterone receptors are expressed sparsely both in glands and stroma, while estrogen receptors are abundant in the glands and absent in the stroma. In 11 of 12 patients an abnormal endometrial development with stromal advancement was observed: this morphological picture of the endometrium could partially be explained only in the four cases presenting high progesterone levels by serum values and endometrial receptor content of estrogen and progesterone. CONCLUSIONS: The abnormal endometrial development in hyperstimulated IVF cycles could only in part be explained by estrogen and progesterone, and other factors have to be considered.

Massive vulvar edema in ovarian hyperstimulation syndrome. A case report.

BACKGROUND: Bilateral vulvar edema associated with severe ovarian hyperstimulation syndrome is described for the first time. CASE: A 28-year-old woman underwent gonadotropin-releasing hormone analogue and gonadotropin treatment for in vitro fertilization and embryo transfer. On day 18 of the cycle, the patient reported mild abdominal discomfort that became severe during the following four days. One the 22nd day of the cycle, bilateral ovarian enlargement and ascites were present. The vulva showed massive edema and fissures. Ovarian hyperstimulation syndrome (OHSS) therapy consisted of human albumin, lactated Ringer's solution and heparin. The vulvar edema was treated with topical hydrocortisone ointment, ice packs and topical gentamycin twice a day. After one week of treatment, the vulva was normal. CONCLUSION: We think that the vulvar edema in this case was the result of decreased oncotic pressure and increased hydrostatic pressure, as occur during OHSS.

Intraoperative ultrasound guidance for operative hysteroscopy. A prospective study.

OBJECTIVE: To evaluate the efficacy and safety of ultrasound (US) guidance as compared to laparoscopic monitoring during operative hysteroscopy. STUDY DESIGN: Prospective, open study including 81 patients undergoing operative hysteroscopy under US guidance for uterine septum and submucous myoma. Clinical and surgical outcomes were compared with those in an historical control group of 45 patients undergoing the same operation under laparoscopic guidance. RESULTS: US guidance proved satisfactory in all patients, and there were no complications due to insufficient visualization of the pelvic structures; in no case was conversion to laparoscopic guidance required. US scanning was most useful in determining the outer limit of the intramural component of submucous partial intramural myoma, allowing complete resection. During metroplasty, US guidance allowed extension of the resection beyond the normal limit conventionally defined by hysteroscopy; none required reintervention. By comparison, in the control group, a second attempt was required because the operation was insufficiently radical in four patients. CONCLUSION: US guidance was used successfully as the only visual aid for hysteroscopic surgery, comparing favorably with laparoscopy in terms of efficacy and safety.