Pregnancy and neonatal outcomes among a cohort of HIV-infected women in a large Italian teaching hospital: a 30-year retrospective study.

The primary study objective was to investigate three decades from 1985 to 2014 of changes in pregnancies among HIV-infected women. The secondary objective was to assess risk factors associated with preterm delivery and severe small-for-gestational-age (SGA) infants in HIV-infected women. A retrospective review of deliveries among pregnant HIV-infected women at the University of Genoa and IRCCS San Martino-IST in Genoa between 1985 and 2014 was performed. Univariate and multivariable analyses were used to study the variables associated with neonatal outcomes. Overall, 262 deliveries were included in the study. An increase in median age (26 years in 1985-1994 vs. 34 years in 2005-2014), in the proportion of foreigners (none in 1985-1994 vs. 27/70 (38·6%) in 2005-2014), and a decrease in intravenous drug use (75·2% (91/121) in 1985-1994 vs. 12·9% (9/70) in 2005-2014) among pregnant HIV-infected women was observed. Progressively, HIV infections were diagnosed sooner (prior to pregnancy in 80% (56/70) of women in the last decade). An increase in combined antiretroviral therapy (cART) prescription during pregnancy (50% (27/54) in 1995-2004 vs. 92·2% (59/64) in 2005-2014) and in HIV-RNA <50 copies/ml at delivery (19·2% (5/26) in 1995-2004 vs. 82·3% (53/64) in 2005-2014) was observed. The rate of elective caesarean section from 1985 to 1994 was 9·1%, which increased to 92·3% from 2004 to 2015. Twelve (10·1%) mother-to-child transmissions (MTCT) occurred in the first decade, and six (8·3%) cases occurred in the second decade, the last of which was in 2000. Preterm delivery (<37 weeks gestation) was 5% (6/121) from 1985 to 1994 and increased to 17·1% (12/70) from 2005 to 2014. In univariate and multivariable logistic regression analyses, advancing maternal age and previous pregnancies were associated with preterm delivery (odds ratio (OR) 2·7; 95% confidence intervals (CI) 1-7·8 and OR 2·6; 95% CI 1·1-6·7, respectively). In the logistic regression analysis, use of heroin or methadone was found to be the only risk factor for severe SGA (OR 3·1; 95% CI 1·4-6·8). In conclusion, significant changes in demographic, clinical and therapeutic characteristics of HIV-infected pregnant women have occurred over the last 30 years. Since 2000, MTCT has decreased to zero. An increased risk of preterm delivery was found to be associated with advancing maternal age and previous pregnancies but not with cART. The use of heroin or methadone has been confirmed as a risk factor associated with severe SGA.

The risk of premalignant and malignant pathology in endometrial polyps: should every polyp be resected?

AIM: There is no wide consensus in the literature on the clinical significance and management of symptomatic and asymptomatic polyps. Aims of the study are to evaluate frequency of premalignant and malignant histo-pathologic features in endometrial polyps resected hysteroscopically and identify clinical parameters able to predict final histopathologic diagnosis. METHODS: Clinical data and pathologic report of 90 consecutive operative hysteroscopies performed on women with endometrial polyps were collected. Frequency of premalignant and malignant histopathologic features on the polyps were calculated and relation to clinical risk factors analyzed. RESULTS: The frequency of premalignant and malignant histopathologic features in polyps was 6.7% and 2.2% respectively. Owing to the small sample size no statistical analysis to detect clinical risk factor for premalignant or malignant histopathologic features could be performed. CONCLUSION: Frequency of premalignant and malignant histopathologic features in symptomatic and asymptomatic patients is not negligible. Reported clinical risk factors for malignant degeneration of endometrial polypoid lesions are the same as those reported for endometrial cancer and are very common in patients with endometrial polyps. Every endometrial polyp should be resected.

Cytological analysis of the distension fluid used during diagnostic office hysteroscopies in patients with suspected endometrial pathology.

OBJECTIVE: Evaluation of the feasibility and usefulness of cytological analysis of the distension fluid used during diagnostic office hysteroscopy in patients with suspected endometrial pathology. METHODS: In 243 consecutive patients undergoing diagnostic hysteroscopy for suspected endometrial pathology a few milliliters of the distension medium used for uterine visualization were collected and sent for cytological analysis. Findings of these "endometrial washings" were compared to visual hysteroscopic impression, endometrial biopsy and uterine histology--when available. RESULTS: Endometrial washings were considered adequate in 227 patients (93.4%). In 12 cases (5.3%) atypical cells were detected: all of these presented either atypical complex hyperplasia or endometrial cancer at the final histological evaluation of the uterus. Four of the 16 (25%) patients diagnosed with endometrial cancer or atypical complex hyperplasia at the final histopathological analysis of the uterus had inadequate washings. No patient with cancer or atypical hyperplasia had negative cytology. CONCLUSIONS: Collection and analysis of the distension fluid is feasible and, when positive, has a remarkable value in the diagnosis of endometrial cancer and its precursors.

Steroid therapy and the endometrium: biological and clinical implications.

The benefits of estrogen replacement therapy in postmenopausal women include increased quality of life, relief from specific symptoms, and the prevention of osteoporosis, genitourinary atrophy, and cardiovascular diseases. Despite these advantages, this therapy has been reported to be associated with an increased frequency of endometrial hyperplasia and adenocarcinoma. In order to evaluate a possible relationship between the histological findings and stroma-derived growth regulators, 19 endometrial samples obtained from women undergoing both percutaneous (n = 11) and oral (n = 8) steroid replacement therapy were processed for histological and immunocytochemical evaluation of estrogen receptor (Er), progesterone receptor (Pr), and epidermal growth factor receptor (EGFr). Transdermal estradiol was given for 21 days and 10 mg medroxyprogesterone acetate (MAP) were added to the last 12 days; conjugated equine estrogens were given for 21 days and 10 mg MAP added to the last 12 days. Endometrial samples were obtained between days 17-18 of the sixth month of therapy. Proliferative and hyperplastic endometria showed immunoreactivity against Er, Pr, and EGFr. Atrophic endometria were always negative by immunocytochemistry. Our results suggest: 1) a relationship between histological findings and the receptor examined; 2) a crucial role for EGF in the regulation of endometrial proliferation.

Computerized colposcopy: results of a pilot study and analysis of its clinical relevance.

OBJECTIVE: To evaluate the clinical usefulness of a computer based system that stores and analyzes high-resolution digital colposcopic images. METHODS: Three hundred patients referred to our institutions for evaluation of abnormal cervical cytology underwent colposcopy with development of digital images. The first 70 patients were used to standardize the system. The images obtained from 188 evaluable patients were analyzed and scored by software according to internationally recognized colposcopic criteria. The results were compared with traditional colposcopic diagnoses and with corresponding histology results using kappa statistics for inter-observer agreement and McNemar test for significance. RESULTS: The exact concordance rate between computer-aided impressions and histology (85.1%, kappa = 0.77) was significantly higher (P < .001) than that observed between traditional colposcopic findings and histology (66%, kappa = 0.40). The computer-assisted colposcopy was much more accurate than traditional colposcopy in diagnosing high-grade lesions (91.2 versus 61.8% of exact concordance, P < .001) as well as normal histology (74.1 versus 34.5%, P < .001), but not significantly different when evaluating low-grade lesions (89.6 versus 86.5%). CONCLUSION: The integration of computer imaging and colposcopy can improve the colposcopic diagnostic accuracy. An inexperienced colposcopist may benefit from computerized support to obtain the most appropriate histologic specimen, and eventually access to distant consultation via modem or through on-line services. An additional advantage is the ability to develop a space-saving permanent record of digitized images readily available to review a patient's cervical history or perform effective programs of quality control in colposcopy.

Endometrial morphology after 12 months of vaginal oestriol therapy in post-menopausal women.

The endometrial effect of long-term vaginal oestriol (E3) therapy for urogenital atrophy was assessed in 23 post-menopausal women. Hysteroscopic and histological examinations were performed in each patient to assess endometrial atrophy before treatment and after 6 and 12 months of therapy (0.5 mg vaginal E3 for 21 days, then 0.5 mg twice weekly). The primary atrophic picture was confirmed at the end of the 6th month in all but one of the patients. In one case, the histology showed an abnormal stromal reaction with no epithelial alterations. Treatment was continued and after the 12th month complete atrophy was confirmed both hysteroscopically and histologically in all patients. Efficacy as regards vaginal and urogenital complaints was good. Our results demonstrate that in women with endometrial atrophy effective and well-tolerated treatment with vaginal E3 can be safely continued for up to 12 months.

The incidental finding of abnormal cervical histology in postmenopausal patients.

A report is supplied on 216 samples of cervical tissue incidentally found in 684 endometrial specimens collected during hysteroscopic examination of postmenopausal women with uterine bleeding and a recent negative Pap smear. We found 43 (19.9%) specimens including cervical tissue with some histologic sign of pathology. Twenty-five (11.6%) had histologic features suggestive for human papillomavirus (HPV) infection, while 18 (8.3%) had cervical intraepithelial neoplasia (CIN). Of the 18 CIN cases, 9 were CIN I, 6 CIN II and 3 CIN III. Altogether, the prevalence of dysplasia in postmenopausal women with recently referred normal cervical cytology was impressive. A significant number of dysplastic lesions (14 out of 18, 77.7%) did not present any histologic sign of HPV. Also, none of the histologic diagnoses of sub-clinical HPV infection was confirmed by the in situ hybridization. Considering the significant prevalence of high grade lesions (9 CIN II and III, 4.2% of the analysed samples) found in this randomly selected patient population, our data strongly suggest the need for a regular follow-up of the transformation zone in all postmenopausal women. Although in women of postmenopausal age some low grade lesions seem to have only a reactive-reparative significance, a more accurate screening procedure, taking into account the peculiar modifications of the menopausal uterine cervix, is advisable.

Endometrial response in sequential cyclic therapy assessed with associated hysteroscopy and histology.

A morphologic study was performed on the endometrium in 37 asymptomatic postmenopausal women under effects of cyclically administered oestrogens. Eighty-seven postmenopausal women were taken as control group. Medroxyprogesterone acetate (MPA), 10 mg daily, was administered in association with two types of oestrogen replacement therapy: conjugated equine oestrogens 0.625 mg (CEE) or transdermal 17 beta-oestradiol 0.05 mg (E2-TTS). Endometrial biopsies were taken under hysteroscopic control before treatment and on days 8-12 of combined therapy at the 6th month. Follow-up at 12 and 18 months was only performed in 8 and 5 patients, respectively, with transdermal 17 beta-oestradiol treatment. Various types of endometrial response were identified from atrophy to hyperplasia and secretory patterns. No atypical hyperplasia was found. All cases of simple or complex hyperplasia showed a regression after increased MPA dosage treatment (20 mg). This work is aimed at investigating the endometrial response during sequential cyclic therapy by using morphologic criteria based on hysteroscopy and histology. A large number of patients with hyperplasia can be detected with target biopsy under hysteroscopy, thus playing an important role in the management of patients during replacement therapy in research protocols.

Vaginal micronized progesterone in continuous hormone replacement therapy. A prospective randomized study.

BACKGROUND: In the non-hysterectomized post-menopausal woman undergoing estrogen replacement therapy, the co-administration of a progestogen is mandatory to counteract the estrogenic proliferative effect on the endometrium. Metabolic and tissue effects of the various progestins vary with dosage and route of administration. This study was performed to evaluate the effects of selected progestins on the lipidic profile and endometrial morphology. METHODS: This is a prospective randomised study including 60 post-menopausal women undergoing hormonal replacement therapy (HRT). All patients received transdermic ethinil-estradiol in a continuous schedule. The utilized progestogens were: medroxyprogesterone acetate (MPA) 10 mg p.o. 12 days/month, transdermic nor-ethisterone acetate (NETA) 0.25 mg integrated in the ethinil-estradiol patches for the last two weeks of each cycle, micronized progesterone (MP) 100 mg transvaginally 12 days/month. RESULTS: None of the tested protocols significantly altered the lipidic profile of this group of patients. We noticed different effects on the estrogen stimulated endometrium elicited by the different progestinic regimens. While the cyclic administration of oral MPA or transdermic NETA more frequently resulted in endometrial atrophy, the trans-vaginal administration of MP more often induced (p<0.005 at six-month and p <0.001 after 1 year) a functional-like secretive endometrium. CONCLUSIONS: Micronized progesterone, cyclically administered in the form of a vaginal cream, offers an acceptable and effective alternative for women on continuous HRT wishing to maintain their monthly cycle.

Human papillomavirus in cervical adenocarcinoma. An in situ hybridization study.

Twenty cervical adenocarcinomas (CACs) in women aged 22 to 71 were investigated by in situ hybridization (ISH) with 6, 11, 16, 18, 31, 35 and 51 HPV biotinylated probes. Two cases, one adenocarcinoma and one adenosquamous carcinoma (in women aged 28 and 40 respectively) showed focal nuclear positivity to 16 HPV Probe in some neoplastic glands. We used ISH, rather than other hybridization techniques, in order to exclude a positivity to viral DNA, due to adjacent squamous epithelium, either normal or metaplastic, and in squamous foci within adenosquamous tumors. Reviewing the literature, we found 33 out of 98 CACs positive to viral DNA by ISH (33.6%). In spite of the differences found from author to author, a relationship between adenocarcinomas of the uterine cervix and HPV infection seems to be possible, as was demonstrated for CIN and invasive cervical carcinomas. These data could explain why the incidence of this neoplasia has tended to increase over the last few years, mainly in younger patients.

Frequency and cause of aborted laparoscopic-assisted vaginal hysterectomy.

STUDY OBJECTIVE: To evaluate the frequency and cause of aborted laparoscopic-assisted vaginal hysterectomies (LAVH) at two hospitals of a major obstetrics and gynecology training program. DESIGN: Retrospective cohort study. SETTING: A university hospital and a university-affiliated county hospital. PATIENTS: Seventy-eight consecutive women who underwent LAVH at our institutions between June 1992 and February 1995. INTERVENTIONS: Data on age, weight, indications for surgery, obstetric and surgical history, concomitant procedures performed, postoperative diagnosis, perioperative complications, operative time, estimated blood loss, uterine weight, and length of hospital stay were collected from patients' hospital records. Univariate analysis of variance to assess statistical significance was performed when appropriate. MEASUREMENTS AND MAIN RESULTS: Eight (11.1%) of 78 procedures were converted to abdominal hysterectomy. The most frequent reason for conversion (5 cases, 6%) was large uterine size with limited mobility and associated inability to visualize the pelvic sidewall structures adequately. The other three procedures were converted because of massive intraperitoneal adhesions (2) and intraoperative severe bleeding (1). The mean uterine weight of these eight women (575 g, range 387-1030 g) was significantly higher than that of patients undergoing successful LAVH (230 g, range 35-612; p <0.03). CONCLUSIONS: In our limited series of 78 patients, only one LAVH was converted to abdominal hysterectomy because of an intraoperative complication. A conversion rate of 11.1% may be appropriate so as to offer the potential benefits of the laparoscopic-assisted vaginal approach to the largest number of women who would otherwise undergo an abdominal hysterectomy.

Biology of nidation and ectopic implantation.

The incidence of ectopic pregnancy has been steadily growing during the past decade; this fact can only partially be related to known factors (PID, use of IUDs, minipill, inductors of ovulation, sterilization reversal). Ectopic pregnancy is still a frequently misdiagnosed pathology; nevertheless, the recent advances in early diagnosis have allowed a decrease in the mortality rate and an improvement in subsequent fertility. In absence of obvious tubal abnormalities it is difficult to assess the cause of an ectopic implantation. Yet the factors regulating and nidation of the embryo in the human are far from clear. The transport of the embryo in the oviductal fluid depends on ciliary beat (generally regarded as the leading factor) and on muscle contractions mainly in the ampullary-isthmic and in the utero-tubal junction, where a sphincter action is stimulated by estrogens and relaxed by progesterone. Other substances (catecholamines, prostaglandins, oxytocin) are thought to be involved in ovum transport, although their role is unclear. Even less is known about local influence of the embryo on the oviduct. During preimplantation and implantation both the embryo and the mother engage in an elaborate interaction, elsewhere referred to as a 'conversation', involving long-and short-range signals. An essential role is played by the endocrine luminal milieu. A local action of estrogens on a progesterone-primed endometrium may be required for either the release of crucial signals for the blastocyst activation, or to make epithelial cells sensitive to the presence of the embryo, thus inducing the decidualization. In some animals, these estrogens are not ovarian, but synthesized by the blastocyst itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of the abnormal papanicolaou smear during pregnancy: lessons for quality improvement.

OBJECTIVE: Our goal in this study was to evaluate the management of pregnant patients with abnormal Papanicolaou smears. MATERIALS AND METHODS: We reviewed the records of 292 patients undergoing colposcopy to evaluate abnormal cervical cytology during pregnancy. RESULTS: A total of 32 (11%) of the subjects had Papanicolaou smears demonstrating atypical glandular cells of undetermined significance; 178 (61%) had low-grade squamous intraepithelial lesions; 69 (23.6%) had high-grade squamous intraepithelial lesions; and 2 (1%) had a malignancy. The first colposcopy was performed most commonly during gestational week 24. Colposcopy showed findings consistent with minor changes in 154 cases (53%) and with major changes in 61 (21%). Only 27 patients (9% of the total) underwent a colposcopically directed biopsy, and 51 (83.6%) of the 61 patients with a colposcopic impression of cervical intraepithelial neoplasia grade 2 or greater did not undergo biopsy. Only 24 (26%) of the 91 patients scheduled for follow-up colposcopy during pregnancy complied, and 123 of the 292 patients (42%) returned for follow-up examinations after delivery. Four patients had an invasive cervical carcinoma diagnosed in the 12 months immediately after delivery. Although the first intrapregnancy colposcopy in two of these patients noted findings consistent with cervical intraepithelial neoplasia grade 2 or greater, none of the four underwent biopsy during pregnancy. CONCLUSIONS: Evaluation of cytological abnormalities is frequently suboptimal during pregnancy. The threshold for colposcopically directed biopsy is often modified during pregnancy in a way that may be harmful to the patient. Extra effort is needed to tailor follow-up to the patient's need and to improve patient compliance.

Potential of endocervical lavage for cytogenetic investigation of fetal cells as determined by in situ hybridization.

Aims: Transcervical samples following endocervical lavage from 28 women undergoing pregnancy termination were analysed in terms of fetal cells content and suitability for in situ hybridization analysis. A non fluorescent protocol of hybridization coupled to specific cytological procedures was used for simultaneous recognition and investigation on syncitiotrophoblast fragments. Methods: A series of endocervical washings was randomised to cytobrushing samples. Cervical washings were performed using variable volumes of physiologic saline solution (2ml, 5ml, 10ml). Single target in situ hybridization for chromosomes 1 and 18 was applied for determining a model of efficiency. Syncitial cells were recognized by means of cytoplasmic and nuclear stainings obtained with Eosin G (Diff-Quik) and haematoxylin respectively. Results: When 5 - 10ml of sterile solution were flushed multiple fragments of syncitio-trophoblast were almost constantly recovered. Conversely using 2ml of flushing solution no syncitia at all could be retrieved. Fetal cells were collected only in 50% of cervical cytobrushing. The per cell hybridization efficiency was on average 50%. Following in situ hybridization, a normal number of signal-products (2) was found in all nuclei analysed. Conclusion: During endocervical washing the amount of volume used is a critical factor to allow successful recovery of fetal cells. By using 5 - 10 ml of injecting solution, enough fetal material was generally obtained from each individual to guarantee the cytogenetic investigation for two chromosomes. The use of Diff-Quik and haematoxylin staining coupled to bright-field microscope facilitate the recognition of syncitia among a highly heterogeneous population of maternal cells. Further studies are ongoing to prospectively evaluate safety of the transcervical approach for sampling and analysis of fetal cells.