Fertility preservation and monitoring in adult patients diagnosed with lymphoma: consensus-based practical recommendations by the Fondazione Italiana Linfomi & Società Italiana della Riproduzione Umana.

Introduction: Fertility preservation (FP) and monitoring has considerable relevance in the multidisciplinary approach to cancer patients. In these consensus-based practical recommendations, the scientific societies Fondazione Italiana Linfomi (FIL) and Società Italiana della Riproduzione Umana (SIRU) reviewed the main aspects and identified the optimal paths which aim to preserve and monitor fertility in patients diagnosed with lymphoma at the different phases of the disease and during long-term survivorship. Methods: For the Panel, eleven experts were selected for their expertise in research and clinical practice on onco-fertility and lymphoma. The Panel's activity was supervised by a chairman. A series of rank-ordering key questions were proposed according to their clinical relevance and discussed among the Panel, focusing on patients diagnosed with non-Hodgkin's lymphomas and Hodgkin lymphoma. Agreement among all the Panelists on the content and terminology of the statements was evaluated by a web-based questionnaire according to the Delphi methodology. Results: From the literature review a total of 78 questions or sentences, divided into the 6 areas of interest, were identified. By applying the Gwet's AC, k was: Section 1: 0,934 (Very good); Section 2: 0,958 (Very good); Section 3: 0,863 (Very good); Section 4: 0,649 (Good); Section 5: 0,936 (Very good); Section 6 raw agreement 100%. Two rounds of Delphi allowed to provide the maximum agreement. All statements were newly discussed in a round robin way and confirmed for the drafting of the final recommendations. Discussion: These recommendations would be useful for onco-hematologists, gynecologists, urologists, and general practice physicians who take care of young lymphoma patients to guarantee an evidence-based oncofertility assessment and treatment during the oncologic pathway.

Serum anti-Müllerian hormone as a marker of ovarian reserve after cancer treatment and/or hematopoietic stem cell transplantation in childhood: proposal for a systematic approach to gonadal assessment.

OBJECTIVE: Female patients treated with alkylating agents in childhood are at risk for ovarian impairment. We aimed at describing the pattern of residual ovarian function in a cohort of survivors of hematological malignancies and/or hematopoietic stem cell transplantation (HSCT) and assessing the relationship between cyclophosphamide equivalent dose (CED) and anti-Müllerian hormone (AMH). DESIGN AND METHODS: Gonadal health was clinically and biochemically assessed in 124 post-menarchal survivors who underwent treatment for pediatric hematological malignancies and/or HSCT between 1992 and 2019. RESULTS: Overt 'premature ovarian insufficiency' (POI) was detected in 72.1 and 3.7% of transplanted and non-transplanted patients, respectively; milder 'diminished ovarian reserve' (DOR) in 16.3 and 22.2%. In non-transplanted patients, increasing CED values were associated with lower AMH-SDS (P = 0.04), with the threshold of 7200 g/m2 being the best discriminator between DOR/POI and normal ovarian function (AUC: 0.75 on ROC analysis) and with an observed decrease of 0.14 AMH-SDS for each CED increase of 1 g/m2. In addition, age at diagnosis ≥10 years played a detrimental role on ovarian reserve (P = 0.003). In the HSCT group, irradiation was associated with a statistically significant reduction in AMH-SDS (P = 0.04). CONCLUSIONS: In non-transplanted patients, CED ≥ 7200 mg/m2 was associated with a DOR, while younger age at diagnosis played a protective role on ovarian reserve. As a result of the data collected, we propose a systematic algorithm to assess iatrogenic gonadal impairment in young female patients exposed to chemo-radiotherapy in childhood for hematological disorders.

Female adolescents and young women previously treated for pediatric malignancies: assessment of ovarian reserve and gonadotoxicity risk stratification for early identification of patients at increased infertility risk.

OBJECTIVES: Childhood and adolescent cancer survivors (CACSs) are at risk of adverse reproductive outcomes. Assessment of follicle-stimulating hormone (FSH) levels is the most common test used to diagnose premature ovarian insufficiency (POI) whereas anti-m|llerian hormone (AMH) and antral follicle count (AFC) have been proposed as ovarian reserve markers. We assessed the correlation between these markers and treatment gonadotoxicity risk (GR) in CACSs. METHODS: A total of 55 female CACSs were enrolled. GR was graded as low, medium, or high according to classifications based on disease and treatments and on cyclophosphamide equivalent dose score. FSH, AMH, and AFC were determined. POI was defined by amenorrhea and FSH>30 IU/L. For remaining patients, diminished ovarian reserve (DOR) was defined by AMH<5th centile. FSH and AFC cut-offs proposed in the literature as DOR markers were also considered (FSH>10 IU/L or >95th centile; AFC<8 or <5th centile). RESULTS: Ovarian reserve results to be compromised in 23 (41.8%) patients: 14 with DOR and 9 with an established POI. Results showed GR classifications to be a good predictor of ovarian reserve, with significantly lower AMH and AFC in the high-risk groups. AFC resulted to be directly correlated with AMH (r=0.75, p<0.001). CONCLUSIONS: In CACSs, GR classifications correlate with post-treatment AMH and AFC. These are useful tools in the early identification of young patients with DOR, who may benefit from reproductive and fertility preservation counseling. Further studies are needed to determine the rate and time of progression from DOR to POI in this population.

A novel de novo partial xq duplication in a girl with short stature, nonverbal learning disability and diminished ovarian reserve - effect of growth hormone treatment and fertility preservation strategies: a case report and up-to-date review.

BACKGROUND: Xq duplication is a rare condition with a very variable phenotype, which could mimic other genetic syndromes involving the long arm of chromosome X. Sometimes short stature and diminished ovarian reserve (DOR) may be present. Treatments with rGH (Recombinant growth Hormon) or with fertility preservation strategies have not been previously described. CASE PRESENTATION: We present the case of a female with a novel de novo Xq partial duplication (karyotype: 46,Xder(X)(qter→q21.31::pter→qter) confirmed by array-CGH analysis. She presented with short stature, Nonverbal Learning Disability, developmental delay during childhood, severe scoliosis, spontaneous onset of menarche and irregular menstrual cycles. AMH (Anti-Müllerian Hormone) allowed detection of a preserved but severely diminished ovarian reserve with a POI (Premature Ovarian insufficiency) onset risk. She was effectively subjected to fertility preservation strategies and rGH therapy. We also reviewed other published cases with Xq duplication, reporting the main clinics characteristics and any adopted treatment. CONCLUSIONS: rGH treatment and cryopreservation in a multidisciplinary approach are good therapeutic strategies for Xq duplication syndrome with short stature and premature ovarian failure.

Selective use of episiotomy: what is the impact on perineal trauma? Results from a retrospective cohort study.

PURPOSE: To evaluate the effects of selective use of episiotomy on perineal trauma. METHODS: We performed a retrospective cohort study on consecutive vaginal deliveries from January 2010 to December 2016. From January 2010 to December 2011 episiotomy was performed liberally, based only on individual midwife/doctor's decision. Since January 2012, a shared selective use of episiotomy policy has been introduced. To evaluate the range of perineal trauma in spontaneous second-degree perineal tears, a sub-classification of second-degree lacerations has been introduced dividing them into two sub-groups: A (smaller than the average episiotomy) and B (spontaneous vaginal tear larger than the average episiotomy). The primary outcomes were the incidence and type of perineal trauma, with the proportion of type A and type B second-degree spontaneous tears under a policy of selective episiotomy. RESULTS: Deliveries not exposed to selective use of episiotomy were 1583 (Group 1), those exposed to selective use of episiotomy were 6409 (Group 2). In Group 2 episiotomy rate decreased, and incidence of intact perineum, first- and second-degree lacerations increased. The incidence of third- and fourth-degree lacerations did not change. Spontaneous second-degree lacerations occurred in 19.4% and 36.8% of women in group 1 and 2, respectively. With a selective episiotomy policy, 88.3% of second-degree tears was classified as type A. CONCLUSIONS: The selective use of episiotomy is clinically feasible and effective. This policy seems to be associated with a lower delivery-related perineal trauma as showed by the sub-classification, that could be a useful tool to monitor obstetric care.

Are we choosing the correct FSH starting dose during controlled ovarian stimulation for intrauterine insemination cycles? Potential application of a nomogram based on woman's age and markers of ovarian reserve.

PURPOSE: To evaluate the potential application of a nomogram based on woman's age and ovarian reserve markers as a tool to optimize the follicle-stimulating hormone (FSH) starting dose in intrauterine insemination (IUI) cycles. METHODS: We conducted a retrospective analysis enrolling 179 infertile women undergoing controlled ovarian stimulation (COS), followed by IUI. Each woman received an FSH starting dose according to clinical decision. After collecting data about COS and IUI procedures, we calculated the FSH starting dose according to the nomogram. The main outcomes measured were women's baseline characteristics, COS, and clinical outcomes. RESULTS: The FSH starting dose calculated by the nomogram was significantly lower than the one actually prescribed (p < 0.001), in only 14.8% of the cycles nomogram calculated a higher starting dose. When gonadotropin dose was decreased during COS, and similarly in case of hyper-response (more than two follicles ≥ 16 mm retrieved), the FSH starting dose calculated by the nomogram would have been lower in most of the cases (81.8% and 48.8%, respectively). Conversely, when gonadotropin dose was increased during COS and in case of low ovarian response (no follicle ≥ 16 mm retrieved), the FSH starting dose calculated by the nomogram would have been lower in most of the cases (64.7% and 100%, respectively); in these groups median anti-Müllerian hormone (AMH) level was 5.62 ng/mL. CONCLUSIONS: The application of this nomogram in IUI cycles would lead to a more tailored FSH starting dose and improved cost-effectiveness, although in PCOS women, particularly the ones with high AMH, it does not seem adequate.

Pre-eclampsia: evidence of altered ventricular repolarization by standard ECG parameters and QT dispersion.

Pre-eclampsia complicates approximately 6-8% of all pregnancies. Epidemiologic studies have demonstrated a relationship between pre-eclampsia and cardiac morbidity and mortality later in life, but the effect of pre-eclampsia on electrical cardiac activity during the acute phase has not yet been understood. The aim of this study was to investigate ECG alterations during pre-eclampsia. Prepartum ECGs of 76 consecutive pre-eclamptic women were compared with those of 76 healthy pregnant women. All of the routine ECG parameters were considered, and ventricular repolarization was assessed by QT interval and QT dispersion (QTd). Pregnancies complicated by pre-eclampsia showed a significant alteration of ventricular repolarization compared with the control group. Among ECG parameters, QT and QTc intervals and QTd were more prolonged in pre-eclamptic women. Multivariate analysis also showed that pre-eclampsia was the only independent determinant of QTd. In conclusion, pre-eclampsia has a significant effect on ventricular repolarization. This alteration could, in part, explain the increased cardiovascular risk of women with a history of pre-eclampsia. Further studies are necessary to confirm the relationship between ventricular repolarization abnormalities and increased cardiovascular risk later in life.