Current status of fertility preservation in a Spanish tertiary public hospital: multidisciplinary approach and experience in over 1500 patients.

PURPOSE: Currently, 15% of gynaecological and 9% of haematological malignancies are diagnosed before the age of 40. The increased survival rates of cancer patients who are candidates for gonadotoxic treatments, the delay in childbearing to older ages, and the optimization of in vitro fertilisation techniques have all contributed to an increased interest in fertility preservation (FP) treatments. This study reviews the experience of the Fertility Preservation Programme (FPP) of a tertiary public hospital with a multidisciplinary approach. METHODS: This retrospective study included all the available (FP) treatments, performed in patients of childbearing age between 2006 and 2022. RESULTS: 1556 patients were referred to the FPP: 332 oocyte vitrification cycles, 115 ovarian cortex cryopreservation with 11 orthotopic autotransplantations, 175 gonadotropin-releasing hormone (GnRH) agonist treatments, 109 fertility-sparing treatments for gynaecological cancer, and 576 sperm cryopreservation were performed. Malignancy was the main indication for FP (the main indications being breast cancer in women and haematological malignancies in men), although non-oncological pathologies, such as endometriosis and autoimmune diseases, have increased in recent years. Currently, the most widely used FP technique is oocyte vitrification, the increase of which has been associated with a decrease in the use of cortex CP and GnRH agonists. CONCLUSIONS: The increase in FP treatment reflects the implementation of reproductive counselling in oncology programmes. A multidisciplinary approach in a tertiary public hospital allows individualised FP treatment for each patient. In recent years, there has been a change in trend with the introduction of new indications for FP and a change in techniques due to their optimisation.

Antral follicle count measured at down-regulation as predictor of ovarian response and cumulative live birth: single center analysis including 2731 long agonist IVF cycles.

OBJECTIVE: Evaluate antral follicle count measured after pituitary suppression (AFCaps) with a GnRH agonist as predictor of ovarian response and cumulative live birth (CLB). METHODS: This study is a large cohort analysis of retrospective data between January 2011 and September 2020 in a tertiary-care university hospital. All first initiated IVF/ICSI cycles in women under 43 years of age for whom AFCaps was registered in our database were included. To evaluate CLB rates (CLBRs), only finalized cycles were analyzed (at least one live birth and/or all embryos transferred), excluding PGT cycles and severe male factor requiring testicular sperm extraction. RESULTS: AFCaps showed a good predictive ability in predicting ovarian response to ovarian stimulation. Predicting poor response, AFCaps presented an area under the receiver-operating characteristic curve (AUCROC) of 0.85 (95% CI 0.83-0.87), for high response prediction, the AUCROC was 0.80 (95% confidence interval [CI] 0.77-0.83).Although AFCaps was statistically higher in patients who achieved at least one live birth (13.6 ± 6.05 vs. 9.79 ± 6.33) and CLBRs per started cycle significantly increase between AFCaps quartiles (15.9%, 36.2%, 45.1% and 52.9%) its ability to predict CLBR was modest, with an AUCROC of 0.67 (95% CI 0.65-0.69). CONCLUSIONS: Women undergoing their first IVF/ICSI cycle following a long agonist GnRH protocol can be counseled with AFCaps measurement about their probability of achieving poor/high response. Based on this marker physicians can personalize ovarian stimulation with the aim of optimizing ovarian response and minimizing its risks. However, AFCaps has failed to predict CLB per started IVF cycle as an isolated marker.

Evaluation of FMR4, FMR5 and FMR6 Expression Levels as Non-Invasive Biomarkers for the Diagnosis of Fragile X-Associated Primary Ovarian Insufficiency (FXPOI).

Female FMR1 (Fragile X mental retardation 1) premutation carriers are at risk for developing fragile X-associated primary ovarian insufficiency (FXPOI), a condition characterized by amenorrhea before age 40 years. Not all women with a FMR1 premutation suffer from primary ovarian insufficiency and nowadays there are no molecular or other biomarkers that can help predict the occurrence of FXPOI. Long non-coding RNAs (lncRNAs) comprise a group of regulatory transcripts which have versatile molecular functions, making them important regulators in all aspects of gene expression. In recent medical studies, lncRNAs have been described as potential diagnostic biomarkers in many diseases. The present study was designed to determine the expression profile of three lncRNAs derived from the FMR1 locus, FMR4, FMR5 and FMR6, in female FMR1 premutation carriers in order: (i) to determine a possible role in the pathogenesis of FXPOI and (ii) to investigate whether they could serve as a biomarker for the diagnosis of FXPOI. FMR4, FMR5 and FMR6 transcripts levels were evaluated in total RNA extracted from peripheral blood by digital droplet PCR and compared between FMR1 premutation carriers with FXPOI and without FXPOI. The diagnostic value of lncRNAs was evaluated by receiver operating characteristic (ROC) analysis. Results revealed a significant association between FXPOI and high expression levels of FMR4. No association was obtained for FMR5 or FMR6. ROC curve analysis revealed that FMR4 can distinguish FMR1 premutation carrier with FXPOI with a diagnostic power of 0.67. These findings suggest a potential role of FMR4 as a possible biomarker for FXPOI.

Comparison between slow freezing and vitrification of ovarian tissue cryopreservation in assigned female at birth transgender people receiving testosterone therapy: data on histological and viability parameters.

PURPOSE: The use of fertility preservation (FP) techniques has significantly increased in recent years in the assigned female at birth (AFAB) transgender population. Oocyte cryopreservation is the established method for FP, but ovarian tissue cryopreservation may be considered an alternative option, especially during gender-affirming surgery (GAS). The slow freezing (SF) cryopreservation technique is the standard method for human ovarian tissue, but recently, several studies have shown good results with the vitrification (VT) technique. The objective of this study was to compare the effectiveness of VT and SF techniques in ovarian tissue from AFAB transgender people. METHODS: This was a prospective study including 18 AFAB transgender people after GAS. Ovarian tissue pieces from each ovary were cryopreserved by SF and VT and compared with fresh tissue. Study by light microscopy (LM) assessed follicular morphology and density. The percentage of surviving and degenerated follicles was studied with the tissue viability test. Oocytes, granulosa cells and stroma were analysed separately by transmission electron microscopy. RESULTS: The VT technique preserves follicle and stromal tissue as well as the SF method, but with some differences. Evaluation by LM showed better follicle preservation with VT, but the ultrastructural study showed the presence of minor damage with both techniques compared to fresh tissue. CONCLUSION: Both cryopreservation techniques are accurate for maintaining the follicular population and stromal tissue. Further studies are needed to determine the impact of VT on ovarian tissue and the subsequent follicular activation mechanisms in AFAB ovarian tissue.

Experiencia con el uso de toxina botulínica en niños con vejiga hiperactiva neurogénica: Una serie de casos / Experience with Botulinum Toxin in Children with Neurogenic Overactive Bladder: A Case Series

Objetivo Describir la experiencia con la administración de inyección de toxina botulínica en niños con vejiga hiperactiva neurogénica refractaria a manejo de primera línea. Materiales y Métodos Estudio observacional descriptivo (serie de casos) que incluyó a 14 niños con diagnóstico de vejiga hiperactiva neurogénica refractarios a tratamiento de primera línea sometidos a administración intravesical de toxina botulínica entre 2015 y 2021; se realizó el seguimiento teniendo en cuenta las variables clínicas, con evaluación de la respuesta y de los eventos adversos. Se reportaron frecuencias absolutas y porcentajes para las variables cualitativas; para las variables cuantitativas, se reportaron medidas de tendencia central y dispersión. Resultados Se incluyeron 6 niños y 8 niñas, con una media de edad 10,1 (desviación estándar [DE]: ± 4,4) años. Todos los pacientes fueron tratados previamente con anticolinérgico y cateterismos limpios intermitentes, con una media de uso de 2,8 (DE: ± 1.0) pañales al día; 11 (78,5%) pacientes tenían antecedente de infección urinaria, 13 (92,8%), estreñimiento, y 2 (15,3%), incontinencia fecal. En la ecografía, 7 (50,0%) pacientes presentaban engrosamiento de las paredes vesicales, y 6 (42,8%), hidronefrosis. Tras el procedimiento, 1 paciente presentó infección urinaria como complicación, 6 presentaron una respuesta completa, 7, respuesta parcial, y 1 paciente no obtuvo respuesta con la primera inyección, con un tiempo promedio efectivo de la terapia 8 (DE: ± 6,3) meses. Una segunda inyección fue necesaria en 6 (42.8%) pacientes, y, de estos, 3 (50%) requirieron una tercera inyección. Conclusión La inyección de toxina botulinica intravesical como terapia de segunda línea de manejo para vejiga hiperactiva neurogénica tiene buenos resultados, con bajas tasas de complicaciones.

Objective To describe the experience with the administration of botulinum toxin injection in children with neurogenic overactive bladder who were refractory to the first-line management. Materials and Methods A descriptive observational study (case series) which included 14 children with a diagnosis of neurogenic overactive bladder who were refractory to the first-line treatment and were aubmitted to the intravesical administration of botulinum toxin between 2015 and 2021. Follow-up was performed taking into account the clinical variables, wth an evaluation of the response and the adverse events. Absolute frequencies and percentages were reported for the qualitative variables; for the quantitative variables, measures of central tendency and dispersion were reported. Results We included 6 boys and 8 girls with a mean age of 10.1 (standard deviation [SD]: ± 4.4) years. All patients were previously treated with anticholinergics and clean intermittent catheterizations, with a mean use of 2.8 (SD: ± 1.0) diapers per day; 11 (78.5%) had a history of urinary tract infection, 13 (92.8%), constipation, and 2 (15.3%), fecal incontinence. On ultrasound, 7 (50.0%) patients presented bladder wall thickening, and 6 (42.8%), hydronephrosis. After the procedure, 1 patient presented urinary tract infection as a complication, 6 presented complete response, 7, partial response, and 1 patient did not obtain a response with the first injection, with an effective mean time of therapy of 8 (SD: ± 6.3) months. A second injection was required by 6 (42.8%) patients, and of these, 3 (50%) required a third injection. Conclusion Intravesical botulinum toxin injection as a second-line management therapy for neurogenic overactive bladder yileds good results, with low rates of complications.

The Follicular Output Rate (FORT) as a method to evaluate transdermal testosterone efficacy in poor responders.

OBJECTIVE: Follicular Output Rate (FORT) is an efficient quantitative and qualitative marker of ovarian responsiveness to gonadotropins. Transdermal testosterone (TT) has been used as adjuvant therapy to gonadotrophins in order to improve ovarian response in poor responders (PR). The aim of this study was to analyze whether TT can improve follicular sensitivity to gonadotropins using FORT. METHODS: This retrospective study, held in a tertiary-care university hospital included 90 PR patients, according to the Bologna criteria. Patients in Group 1 (n = 46) received transdermal application of testosterone preceding gonadotrophin ovarian stimulation under pituitary suppression. In Group 2 (n = 44) ovarian stimulation was carried out with high-dose gonadotrophin in association with minidose GnRH agonist protocol. We analyzed ovarian stimulation parameters and IVF outcomes. We determined antral follicle count (AFC) (3-8 mm) before ovarian stimulation, pre-ovulatory follicle count (PFC) (16-22 mm) and the day of hCG administration. We calculated the FORT using the PFCx100/AFC ratio. RESULTS: Baseline characteristics and ovarian reserve parameters were similar in both groups. FORT and oocytes retrieved were significantly higher in group 1 vs group 2. There were no significant differences in pregnancy rates. In group 1 there was a significant correlation between FORT and AFC. CONCLUSIONS: This study suggests that the potential beneficial mechanism of TT in poor responder patients may be based on increasing the antral follicle sensitivity to gonadotrophin. FORT is an excellent tool to demonstrate this.

Prognostic Factors for Inguinal Lymph Node Involvement and Tumor Recurrence in Squamous Cell Carcinoma of the Penis / Factores pronósticos de compromiso ganglionar inguinal y recaída tumoral en carcinoma escamocelular de pene

Zoom Image Abstract Introduction Penile carcinoma is an aggressive disease with catastrophic consequences that frequently lead to death. Therefore, further knowledge on the prognostic factors that can help identify patients in need of more aggressive treatments becomes essential. Objective To identify the prognostic factors for lymph node (LN) involvement and tumor recurrence in patients diagnosed with squamous cell carcinoma of the penis (SCCP). Methods A retrospective cohort study was conducted. Patients diagnosed and treated for SCCP at Instituto Nacional de Cancerología between 2008 and 2015 were included in the sample. Cases in which no information on recurrence was available for the follow-up were excluded, as well as patients with no initial pathology and those getting penile reconstructions after cancer. Relevant data was retrieved from the medical records of each patient, and a descriptive analysis was performed. Subsequently, this data was used to apply a logistic regression model to determine the potential clinical and histopathological prognostic factors. Results A total of 104 patients were included in the present study. The average age of the sample was 59 years, while the follow-up averaged 24 months per patient. Inguinal lymphadenectomy was performed on 61 patients (59%) during the follow-up. The logistic regression model showed that lymphovascular invasion (odds ratio [OR]: 6.7; 95% confidence interval [95%CI]: 1.2­35) and poor tumor differentiation (OR: 17; 95%CI: 3.2­92) were associated with tumor recurrence. Likewise, the lymphadenectomy procedures showed that lymphovascular invasion was associated with LN involvement (OR: 3.3; 95%CI: 1.1­10). Conclusion Lymphovascular invasion was the strongest prognostic factor observed in our sample, aiding in the prediction of inguinal LN involvement and tumor recurrence in SCCP patients

Introduccion El cáncer de pene es una enfermedad agresiva con consecuencias catastróficas que frecuentemente llevan a la muerte. Por lo tanto, es esencial un mayor conocimiento sobre los factores pronósticos que pueden ayudar a identificar a los pacientes que necesitan tratamientos más agresivos. Objetivo Identificar los factores pronósticos patológicos de compromiso ganglionar inguinal y recaída tumoral en pacientes con carcinoma escamocelular de pene. Métodos Se realizó un estudio de cohorte retrospectivo. Se incluyeron en la muestra pacientes diagnosticados y tratados por carcinoma escamocelular de pene (SCCP) en el Instituto Nacional de Cancerología entre 2008 y 2015. Los casos en los que no había información sobre la recurrencia en el seguimiento fueron excluidos, así como los pacientes sin patología inicial y aquellos que reciben reconstrucciones del pene después del cáncer. Se recuperaron los datos relevantes de los registros médicos de cada paciente, y una descripción fue realizada. Posteriormente, estos datos se utilizaron para aplicar un modelo de regresión logística para determinar los posibles factores pronósticos clínicos e histopatológicos. Resultados Un total de 104 pacientes fueron incluidos en el estudio. La edad promedio de la muestra fue de 59 años, mientras que el seguimiento promedió fue de 24 meses por paciente. La linfadenectomía inguinal se realizó en 61 pacientes (59%) durante el seguimiento. El modelo de regresión logística mostró que la invasión linfovascular (odds ratio [OR]: 6,7; intervalo de confianza del 95% [IC 95%]: 1,2­35) y la pobre diferenciación tumoral (OR: 17; IC 95%: 3,2­92) se asociaron con recurrencia tumoral. Así mismo, los procedimientos de linfadenectomía mostraron que la invasión linfovascular se asoció con afectación de LN. (OR: 3,3; IC 95%: 1,1-10). Conclusión La invasión linfovascular es el factor pronóstico independiente más importante que se asocia de manera independiente con compromiso ganglionar inguinal positivo y recaída tumoral.

Comparison of GnRH agonist versus luteal estradiol GnRH antagonist protocol using transdermal testosterone in poor responders.

OBJECTIVE: Transdermal testosterone has been used in different doses and in different stimulation protocols in poor responders. The aim of the present study is to compare the luteal estradiol/GnRH antagonists protocol versus long GnRH agonists in poor responder patients according to the Bologna criteria, in which transdermal testosterone has been used prior to the stimulation with gonadotropins. METHODS: In this retrospective analysis, a total of 141 poor responder patients according to the Bologna criteria were recruited. All patients were treated with transdermal testosterone preceding ovarian stimulation with gonadotropins during 5 days. In 53 patients we used the conventional antagonist protocol (Group 1). In 88 patients (GrH pituitary suppression was achieved by leuprolide acetate according to the conventional long protocol (Group 2). We analyzed the ovarian stimulation parameters and IVF outcomes. RESULTS: Comparing groups 1 and 2, there were no significant differences between cancellation rates and number of oocytes retrieved. However the total gonadotropin dose used and the mean length of stimulation were significantly lower in group 1 when compared to group 2. There were no significant differences in pregnancy outcomes; however, there was a slight increase in the implantation rate in group 1 vis-a-vis group 2, although statistical significance was not achieved. CONCLUSION: TT in poor responder patients can be effective both with the conventional agonist's long protocol and with the conventional antagonist's protocol. However, short regimes with previous estradiol antagonists in the luteal phase facilitate ovarian stimulation by shortening the days of treatment and the consumption of gonadotropins.

Congenital Posterior Urethral Fistulae: Literature Review and Case Report.

Congenital posterior urethral-perineal fistula is an abnormal communication extending from the posterior urethra to the perineal skin. We present the case of an 11-year-old boy who had recurrent febrile urinary tract infections and abnormal dribbling of urine from the perineum. Fistulogram showed a paraescrotal fistula tract, which was then surgically excised. During the 10 months of follow-up, the patient remained asymptomatic without recurrence of urinary pathology.

Age, independent from ovarian reserve status, is the main prognostic factor in natural cycle in vitro fertilization.

OBJECTIVE: To analyze natural cycle IVF (NC-IVF) results according to patient age, ovarian reserve status following the Bologna criteria, cause of infertility, and modification of the cycle with the use of GnRH antagonist. DESIGN: Retrospective cohort study. SETTING: Tertiary-care university hospital. PATIENT(S): Nine hundred forty-seven natural cycles carried out in 320 patients. INTERVENTION(S): Analysis of 947 NC-IVF outcomes performed in one single center between January 2010 and December 2014. MAIN OUTCOME MEASURE(S): Pregnancy rates per cycle started, per ET, and per patient, as well as ongoing pregnancy rate at a minimum of 12 weeks of gestation. RESULT(S): Among the three age groups analyzed (≤35 years, 36-39 years, and ≥40 years), pregnancy rates per cycle were significantly lower in the older group of patients (11.4% vs. 11.6% vs. 5.9%). In addition, miscarriage rate (7.7% vs. 34.4% vs. 50%) and ongoing pregnancy rate (10.6% vs. 7.6%vs. 3.0%) were negatively affected by patient age. However, no differences were observed according to patient ovarian reserve status, cause of infertility, or modification of the cycle with GnRH antagonist. The multivariate logistic regression confirmed that patient age was the only variable that could predict pregnancy in NC-IVF cycles (odds ratio, 0.93; 95% confidence interval, 0.88-0.98). CONCLUSION(S): NC-IVF is a feasible and "patient-friendly" option to be offered to young patients, independent of their ovarian reserve status.

Risk of thromboembolic events after recurrent spontaneous abortion in antiphospholipid syndrome: a case-control study.

OBJECTIVE: To investigate whether patients having antiphospholipid syndrome (APS) as the only aetiological factor for recurrent spontaneous abortion (RSA) are at increased risk of thrombosis later in life. METHODS: A case-control study at a tertiary university referral centre. The study group consisted of 57 primary APS and RSA women (APS-RSA group). Control groups included: 86 patients with RSA of unknown aetiology (uRSA group), 42 patients with RSA and thrombophilic genetic defects as the only aetiologic factor for RSA (tRSA group) and 30 antiphospholipid antibody (aPL) positive but otherwise healthy women (aPL group). The main measurement was the thrombosis rate after long-term follow-up. RESULTS: APS-RSA patients had a significantly higher 12-year cumulative thrombotic incidence rate compared with the three comparator groups (19.3% vs 4.8%, 0.0% and 0.0%, respectively (log rank), p<0.001). Patients in the APS-RSA group had 25.6 thrombotic events per 1000 patient-years (95% CI 12.8 to 45.9). The OR of thrombosis in relation to the presence (APS-RSA group) or absence (uRSA and tRSA groups) of aPL in patients with RSA was 15.06 (95% CI 3.2 to 70.5). CONCLUSIONS: Our data indicate that a history of RSA associated with aPL is a risk factor for subsequent thrombosis in the long term.

Estudio de la Dinamica en Familias con Hijos/as con Sindrome de Down / Study the Dynamics in Families With Children With Down Syndrome

El propósito de la investigación es describir las características de la dinámica en familias con hijo/as con Síndrome de Down, a partir de las etapas emocionales, funciones de la familia y expectativas. El estudio es de alcance cualitativo, descriptivo, con entrevistas en profundidad a 6 familias. Los resultados señalan que cada persona atraviesa por diferentes sentimientos ante la situación de discapacidad. El proceso de afrontamiento parece repercutir en las acciones de atención y cuidado, y todos los miembros de la familia participan en dichas acciones. Las expectativas de futuro, giran alrededor del bienestar y autonomía del hijo/a. Por tanto, las características de la dinámica familiar citadas se encuentran vinculadas.

The goal of the research is to describe the characteristics of the dynamics in families with children with Down syndrome, including the emotional stages, family roles and expectations. This is a qualitative, descriptive study, with in-depth interviews to six families. The research results indicate that each person goes through different feelings about the situation of disability. The process of coping seems to affect the actions of attention and care of the person with Down syndrome, and all family members are involved in these actions. The expectations of parents towards their children's future revolve around the welfare and their child"s autonomy. Therefore, the mentioned characteristics of the family dynamics are linked.

Day-5 inhibin B serum concentrations and antral follicle count as predictors of ovarian response and live birth in assisted reproduction cycles stimulated with gonadotropin after pituitary suppression.

OBJECTIVE: To investigate the usefulness of day-5 inhibin B and antral follicle count (AFC) in predicting ovarian response and live birth in the first cycle of assisted reproduction. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENT(S): Ninety-eight infertile women treated with in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) comprising 72 normal responders and 26 poor responders. INTERVENTION(S): Ovarian stimulation with gonadotropin-releasing hormone agonist-gonadotropin treatment. MAIN OUTCOME MEASURE(S): Basal ultrasonographic (AFC, total ovarian volume) and basal (follicle-stimulating hormone, estradiol, and inhibin B) and stimulation day-5 (estradiol, inhibin B) hormone parameters. RESULT(S): The AFC had the best predictive value among the basal variables for outcome of ovarian stimulation. Among the dynamic hormone measurements, day-5 inhibin serum measurement emerged as the best predictive variable of poor response in IVF-ICSI cycles, but it was not statistically significantly better than basal AFC. The association of day-5 inhibin B with live-birth rate was statistically significant and stronger than the effect of any other variable investigated. CONCLUSION(S): Basal AFC and day-5 inhibin B have similar predictive properties for ovarian response in assisted reproduction cycles stimulated with gonadotropin after pituitary suppression, but day-5 inhibin B is a superior predictor of live birth.

Spanish post-menopausal women's viewpoints on hormone therapy.

OBJECTIVE: The purpose of this study was to identify women's socio-demographic and climacteric factors, as well as other variables related to health care, associated with the prescription of the treatment during menopause and to investigate the prevalence of certain conditioning factors in early discontinuation in women aged 40-65 years in a population of post-menopausal women in Spain. STUDY DESIGN: Cross-sectional survey. SETTING: Four of the most inhabited cities in Spain (Madrid, Barcelona, Seville and Valencia). POPULATION: A total of 270 symptomatic post-menopausal women. METHODS: A personal interview with a semi-structured questionnaire specifically designed to collect information on treatments for climacteric-related complaints. MAIN OUTCOME MEASURES: The reasons for HRT, the evaluation of alternative therapies, the reasons for choosing one therapy or another and reasons for discontinuation. RESULTS: Of all the subjects included, 180 were still taking any type of treatment and 90 were former HRT users or had never used HRT. Among the latter, 43% of women expressed fear of the side effects and 38% gave the risk of breast cancer as the main reason for not using HRT. Of them, 58% receive phytoestrogens. Media and negative data from medical journals influenced this attitude in 67% of the women. On the other hand, only 9.4% of HRT users were reluctant to receive the therapy and the main reasons for maintaining HRT were its efficacy against climacteric symptoms, medical prescription and life quality. CONCLUSIONS: Side effects and fear of cancer were the most common reasons for not using HRT; and medical prescription, symptomatic improvement and quality of life were the main reasons for using it. Negative data from journals have an important effect on women's attitudes to HRT.