In male Hodgkin lymphoma patients, impaired fertility may be improved by non-gonadotoxic therapy.

The outcome of patients with Hodgkin lymphoma (HL) has improved significantly in recent years, and now attention is increasingly being focused on the well-being of these young patients. This study aimed to analyse the influence of HL and its treatment on the spermatogenic status of 46 male HL patients with available spermiograms, treated between 2008 and 2016. Analysing prognostic factors at diagnosis, we found that the number of spermatozoa was reduced in stage III-IV; motility and vitality were reduced in stage III-IV and in the presence of B symptoms; and abnormal forms were increased in patients with elevated erythrocyte sedimentation rate (ESR) and low albumin. Furthermore, we found that haematopoietic stem cell transplantation (HSCT) was associated with a severe impairment of fertility in terms of sperm motility. In HL-treated patients who did not undergo HSCT we found a statistically significantly improved fertility in terms of motility. In this study, we found that HSCT induced infertility in the majority of male patients with HL, but that first-line treatment could improve the impaired fertility status caused by disease. Further studies are needed in larger case series to investigate risk factors for impaired fertility at HL diagnosis and after treatment.

Altered Gene Expression Encoding Cytochines, Grow Factors and Cell Cycle Regulators in the Endometrium of Women with Chronic Endometritis.

To evaluate the expression of genes encoding cytokines, grow factors and cell cycle regulators in the proliferative endometrium of women with chronic endometritis (CE) compared to controls. We performed a case-control study on seven women with CE as diagnosed by hysteroscopy and histology (Cases) compared to six women without CE (Controls). All women underwent diagnostic hysteroscopy plus endometrial biopsy during the mid-proliferative phase of the menstrual cycle. Endometrial samples were divided into two different aliquots for histological and molecular analyses. The endometrial expression profile of 16 genes encoding proteins involved in the inflammatory process, proliferation and cell cycle regulation/apoptosis was assessed by using high-throughput qPCR. Study endpoints were between-group differences in the expression of VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1, BAX and IL12. RESULTS: VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1 were significantly overexpressed in women with CE compared to controls, while BAX and IL12 had similar expression between groups. In women with CE, we found an altered endometrial expression of genes involved in inflammatory, cell proliferation, and apoptosis processes. The dominance of proliferative and anti-apoptotic activity in CE may potentially promote the development of polyps and hyperplastic lesions.

Chronic endometritis and altered embryo implantation: a unified pathophysiological theory from a literature systematic review.

PURPOSE: Chronic endometritis (CE) is a frequent hysteroscopic and histological finding which affects embryo transfer implantation during IVF-ICSI cycles. In particular, CE impairs proper decidualization and, subsequently, implantation. Although this correlation has been clearly clarified, a pathophysiological explanation assembling all the studies performed has not been elucidated yet. For this reason, we have structured a systematic review considering all the original articles that evaluated a pathological element involved in CE and implantation impairment. METHODS: The authors searched electronic databases and, after screening, collected 15 original articles. These were fully scanned and used to create a summary pathway. RESULTS: CE is primarily caused by infections, which lead to a specific cytokine and leukocyte pattern in order to prepare the uterus to fight the noxa. In particular, the immunosuppression requested for a proper semi-allogenic embryo transfer implantation is converted into an immunoreaction, which hampers correct embryo implantation. Moreover, endometrial vascularization is affected and both irregular vessel density and luminal thickening and thrombosis reduce what we have first identified as endometrial flow reserve. Finally, incorrect uterine wave propagation could affect embryo contact with decidua. CONCLUSION: This is the first summary of evidence on CE pathophysiology and its relationship with infertility. Understanding the CE pathophysiology could improve our knowledge in embryo transfer success.

Pregnancy rate and outcome of pregnancies in long-term survivors of Hodgkin's lymphoma.

Thanks to the increased number of young survivors of Hodgkin's lymphoma (HL), management of the pregnancies of women who have a history of exposure to chemotherapies and radiation therapy is becoming increasingly common. Many patients and clinicians are worried that pregnancy after the diagnosis of HL may increase the risk of relapse, despite a lack of empirical evidence to support such concerns. In the present study, we included 89 women diagnosed with HL between 2006 and 2015 under the age of 50 years, who were in complete remission and alive without relapse > 1 year after treatment. We determined the pregnancy rate, time to pregnancy, and the disease-free survival. We found no evidence of significant impairment of the fertility of female HL long-term survivors and no evidence that a pregnancy increases the relapse rate among women in remission from HL. Survivors of HL need to consider a range of factors when deciding on future reproduction.

Dynamics of the development of multiple follicles by early versus late hCG administration in ART program.

OBJECTIVE: To evaluate, in patients stimulated with recombinant FSH and GnRH antagonists, whether triggering the final maturation of oocytes affects IVF outcomes. STUDY DESIGN: Five hundred and six IVF procedures were divided into three groups according to the timing of hCG administration: when at least 2 follicles reached the diameter of 17 mm, at least 2 follicles reached 18 mm and at least 2 follicles reached 20 mm. The main outcome was the number of mature oocyte that was the dependent variable of a multivariate model whose independents were, age, AFC, hCG timing, E2 levels at hCG day, number of follicles in different categories of dimension. Secondary endpoints were to compare fertilization, implantation and pregnancy rates in a multilevel multivariate model whose covariates were age, BMI, AFC, embryo quality and cause of infertility. RESULTS: Timing did not result a statistically significant factor influencing the number of oocytes collected, which was influenced by age, AFC, number of follicles between 12.1 and 15.9 mm and E2 levels. Implantation rate and pregnancy rate appear to be affected only by embryo quality. CONCLUSION: The number of oocytes collected and the probability of pregnancy are not associated with the time of hCG administration.

Fertility preservation in males with cancer: 16-year monocentric experience of sperm banking and post-thaw reproductive outcomes.

BACKGROUND: Anticancer treatments can impair male fertility. Cryopreservation of semen is an efficient procedure for fertility preservation. The aim of this study was to evaluate pre-freeze semen parameters among the various types of cancer, post-thaw sperm viability and reproductive outcome of samples used for assisted reproductive treatment (ART). METHODS: This study included 721 men with cancer that had their semen cryopreserved in our bank in 1999-2015. Semen analysis and cryopreservation were performed before the start of antineoplastic treatment, according to the World Health Organization recommendations, European Commission and Italian law. RESULTS: Among the 721 patient, 196 had seminoma of the testis, 173 Hodgkin's lymphoma, 108 mixed testicular tumors, 89 germ cell tumors, 67 other tumors, 46 hematological tumors, and 42 non-Hodgkin's lymphoma. The mean age of patients was significantly lower in Hodgkin's lymphoma compared to other tumors. Statistically significant lower volume, sperm count and number of straws stored were observed respectively in Hodgkin's lymphoma, mixed testicular tumor and hematological tumors. Nineteen patients used their frozen semen for 20 ART cycles. After thawing a significant reduction of motility and vitality was recorded. A lower fertilization rate was observed in patients affected by testicular tumor and lymphoma (35.42% and 50%) compared with other cancers (71.43%). No significant differences were observed in terms of cleavage and implantation rates. A total of five pregnancies and seven healthy newborns were achieved. CONCLUSIONS: Fertility preservation before gonadotoxic therapy is of great importance to patients with cancer and must be indicate before the start of treatment.

The Effects of Chronic Lifelong Activation of the AHR Pathway by Industrial Chemical Pollutants on Female Human Reproduction.

Environmental chemicals, such as heavy metals, affect female reproductive function. A biological sensor of the signals of many toxic chemical compounds seems to be the aryl hydrocarbon receptor (AHR). Previous studies demonstrated the environmental of heavy metals in Taranto city (Italy), an area that has been influenced by anthropogenic factors such as industrial activities and waste treatments since 1986. However, the impact of these elements on female fertility in this geographic area has never been analyzed. Thus, in the present study, we evaluated the AHR pathway, sex steroid receptor pattern and apoptotic process in granulosa cells (GCs) retrieved from 30 women, born and living in Taranto, and 30 women who are living in non-contaminated areas (control group), who were undergoing in vitro fertilization (IVF) protocol. In follicular fluids (FFs) of both groups the toxic and essential heavy metals, such as chromiun (Cr), Manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), cadmium (Cd) and lead (Pb), were also analyzed. Higher levels of Cr, Fe, Zn and Pb were found in the FFs of the women from Taranto as compared to the control group, as were the levels of AHR and AHR-dependent cytochrome P450 1A1 and 1B1; while CYP19A1 expression was decreased. The anti-apoptotic process found in the GCs of women fromTaranto was associated with the highest levels of progesterone receptor membrane component 1 (PGRMC1), a novel progesterone receptor, the expression of which is subjected to AHR activated by its highest affinity ligands (e.g., dioxins) or indirectly by other environmental pollutants, such as heavy metals. In conclusion, decreased production of estradiol and decreased number of retrieved mature oocytes found in women from Taranto could be due to chronic exposure to heavy metals, in particular to Cr and Pb.

Anti-laminin-1 antibodies in serum and follicular fluid of women with Hashimoto's thyroiditis undergoing in vitro fertilization.

The aim of this study is to evaluate the presence of anti-laminin-1 antibodies (aLN-1) in sera and follicular fluid (FF) of infertile women affected by Hashimoto's thyroiditis (HT) undergoing in vitro fertilization (IVF) and its impact on oocyte maturation and IVF outcome. aLN-1 were measured by a home-made enzyme linked immunosorbent assay (ELISA) in: (1) sera and FF from 44 infertile women affected by HT (HTIW) with tubal factor or male factor as primary cause of infertility; (2) in sera and FF from 28 infertile women without HT, with tubal factor or male factor as cause of infertility (infertile controls-ICTR); and (3) in sera from 50 fertile women (FW). aLN-1 serum levels were significantly higher in HTIW when compared with both fertile women and ICTR (P <0.001and P <0.01, respectively). Assuming as cutoff the 99th percentile of values obtained in sera of FW, 43.2% of HTIW and 3.6% of ICTR were aLN-1 positive (P = 0.0001). Also aLN-1 detected in FF from HTIW were significantly higher in comparison with those found in FF of ICTR (P = 0.006). In HTIW, metaphase II oocyte count showed inverse correlation with both serum and FF aLN-1 levels (r = 0.34, P = 0.02 and r = 0.33, P = 0.03, respectively). Implantation and pregnancy rates were significantly lower in HTIW (7.9% and 9.1%, respectively) when compared with ICTR (23% and 31.1%, respectively) (P = 0.015 and P = 0.03, respectively). Our results demonstrated for the first time the presence of aLN-1 in a relevant percentage of HTIW and suggest that these auto-antibodies may impair IVF outcome.

Ultrasonographic and hysteroscopic outcomes of uterine scar healing after cesarean section: comparison of two types of single-layer suture.

AIM: A common anatomical consequence of low-segment cesarean section is the presence of a pouch on the anterior uterine wall that can be detected by sonography or hysteroscopy. Different suturing techniques have been compared (single vs double layer) and showed no substantial differences. This prospective longitudinal study was aimed at evaluating the outcome of the cesarean scar, comparing two different types of single-layer sutures by transvaginal ultrasound and hysteroscopy. MATERIAL AND METHODS: The study sample consisted of two groups of 30 singleton primiparae at term who delivered by elective low segment cesarean section. In the first group, uterine closure was done with locked continuous single-layer sutures and in the second group, with single-layer interrupted sutures. Patients were assessed by transvaginal ultrasound and hysteroscopy, between the 6th and the 12th month after delivery, and again at the 24th month. Ultrasound measurements were made of the pouch area, if present. RESULTS: A bell-shaped uterine wall defect was seen at ultrasound in 36 (85.71%) of 42 patients who completed the follow up at the 24th month. It was larger in the group of patients with closure by continuous sutures (6.2 [2.1-14.7] mm2) as compared to interrupted sutures (4.6 [1.9-8.2] mm2, P = 0.03). Hysteroscopy confirmed the presence of the wall defect in all 36 cases, but different hysteroscopic outcomes were observed. CONCLUSION: Locked continuous sutures seem to cause a larger defect as compared to interrupted sutures, probably due to a greater ischemic effect exerted on the uterine tissue.

Are active labour and mode of delivery still a challenge for extremely low birth weight infants? Experience at a tertiary care hospital.

OBJECTIVE: This study was to evaluate the impact of mode of delivery and timing of caesarean section in extremely preterm births, below 28 weeks of gestation, on long-term survival and psychomotor outcomes. STUDY DESIGN: This was a single-centre retrospective cohort study of 84 cases of extremely low birth weight infants with complete maternal, obstetrical and neonatological information. Mortality and survival with neurological disabilities at 18 months of life were considered outcome measures. RESULTS: Forty percent of deliveries were at or less than 25 weeks of gestation and birth weight was

Non-puerperal uterine inversion due to uterine sarcoma.

BACKGROUND: Uterine inversion is a very rare pathological condition that usually occurs in puerperium. Non- puerperal uterine inversion is exceptional and to our knowledge only a few cases of uterine inversion due to a uterine sarcoma have been reported. CASE REPORT: A 79-year-old woman, gravida 0, para 0, presented with vaginal bleeding. Pelvic examination under anesthesia revealed a huge mass coming from the cervix filling the vagina to the introitus, and rectal examination could not identify the uterus. Diagnosis of uterine inversion was made and the patient was submitted to total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node sampling. The postoperative course was uneventful and the patient was discharged on the 5th postoperative day. She underwent postoperative pelvic radiation, and no recurrence was found during the 19-month follow-up period. CONCLUSION: Chronic non-puerperal uterine inversion can be considered a rare complication of malignant mixed mullerian tumor of the uterus.

The role of office hysteroscopy in menopause.

We evaluated the efficacy of office hysteroscopic treatment of benign intrauterine pathologies using 5F mechanical instruments (scissors, grasping forceps). Subjects were 4863 women who underwent the procedure without analgesia or anesthesia. We treated cervical and endometrial polyps (0.2-3.7 cm), intrauterine adhesions, and anatomic impediments. At 3 months postoperatively, pathology persisted in 364 women (5.6%). Many operative procedures may be performed in the office setting with simple instruments, provided that correct indications are observed.