Minimum number of mature oocytes needed to obtain at least one euploid blastocyst according to female age in in vitro fertilization treatment cycles.

OBJECTIVE: To find a useful tool for estimating the minimum number of metaphase II (MII) oocytes needed to obtain at least one euploid blastocyst according to female age. DESIGN: Retrospective analysis of in vitro fertilization (IVF) treatment cycles with preimplantational genetic testing for aneuploidies (PGT-A) performed over 5 years in IVIRMA Valencia (Spain), January 2017-March 2022. Approval from the Institutional Review Board of IVI Valencia (2204-VLC-040-CR). SETTING: Private infertility clinic in Spain. PATIENTS: Eligible patients were undergoing their first IVF-PGT-A treatment cycle, in which at least one MII oocyte was obtained, regardless of oocyte and semen origin. Oocyte donation cycles were included in the donor group (≤34 years old). Treatment cycles from women with their own oocytes were selected only when the oocytes were aged ≥35 years (patient group). Only trophoectoderm biopsies performed on days 5 or 6 of development and analyzed using next-generation sequencing were included. Preimplantational genetic testing for aneuploidy cycles because of a known abnormal karyotype were excluded. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Number of MII oocytes needed to obtain one euploid blastocyst according to female age. RESULTS: A total of 2,660 IVF-PGT-A treatment cycles were performed in the study period in the eligible population (patients group = 2,462; donors group =198). The mean number of MII oocytes needed to obtain one euploid blastocyst increased with age, as did the number of treatment cycles that did not get at least one euploid blastocyst. An adjusted multivariate binary regression model was designed using 80% of the patient group sample (n = 2,462; training set). A calculator for the probability of obtaining at least one euploid blastocyst was created using this model. The validation of this model in the remaining 20% of the patient group sample (n = 493; validation set) showed that it could estimate the event of having at least one euploid blastocyst with an accuracy of 72.0%. CONCLUSIONS: Our results show a preliminary model capable of predicting the number of MII oocytes needed to obtain at least one euploid blastocyst according to female age, calculated with the largest database of IVF-PGT-A treatment cycles ever used for this purpose, including only treatment cycles using next-generation sequencing on trophoectoderm biopsies. Once this model has been properly validated, it could help with decision-making for both clinicians and patients coming to an infertility clinic.

Do Popular Diets Impact Fertility?

Infertility affects 15% of the population in developed countries, and its prevalence is increasing. Fertility can be influenced by different factors. Although key factors like maternal age cannot be changed, there is growing evidence that other modifiable factors, such as diet, can have an impact on fertility. Diet has become increasingly important in recent years for a number of reasons: the new trend toward a healthy lifestyle, the higher prevalence of certain digestive disorders, a lack of time that leads people to consume more prepared and processed food, and personal choice to not eat meat, among others. To meet these needs, several diets have recently become popular, such as the Mediterranean diet, known as the gold standard of health; the DASH diet, known for preventing hypertension; the Western diet, characterized by processed food; the ketogenic diet, characterized by low carbohydrate intake; and the vegetarian diet, which is the choice for people who do not eat meat or animal by-products. Diets present a unique composition characterized by the presence or absence of specific nutrients, which have also been associated with male and female fertility individually. This review assesses the impact of these diets and of macro- and micronutrients on both female and male fertility.

Respiratory syncytial virus incidence and typing in the last six seasons in the north of Spain (Asturias). Genetic characterization during the SARS-CoV-2 pandemic.

Respiratory syncytial virus is associated with lower respiratory tract infections. As several types and genotypes can circulate at the same time, genomic characterization is important for timely epidemiological control and treatment measures. In the last 6 seasons (2017-2023), 191 236 nasopharyngeal swabs were processed for respiratory viruses to determine the etiology of acute respiratory infections, describe the incidence and distribution of RSV types and enrich the data of epidemiological molecular studies on RSV in Spain. The incidence of RSV reached 7% in the pre-pandemic season. RSV was most frequent in children under 5 years of age (12.6%), but was also significant in those over 70 years of age (5.63%). The measures taken to control SARS-CoV-2 infection were useful for RSV control and the incidence decreased to 1.8%, but caused a change in the types. Pre-pandemic, the majority circulating types were RSV-B/RSV-B/RSV-A and in the pandemic it was RSV-B/RSV-B. In the last season, RSV-B and RSV-A were detected in the same proportion. Genetic characterization showed three new clades. This has been taken into account to understand the epidemiology as well as the development of therapeutic and preventive strategies.

Luteal phase support using micronized vaginal progesterone as pessaries or capsules in artificial cycles: is there any difference?

RESEARCH QUESTION: Is there a difference between the proportion of patients with serum progesterone <8.8 ng/ml on the day of embryo transfer when micronized vaginal progesterone (MVP) for luteal phase support (LPS) is given as pessaries versus capsules? DESIGN: This retrospective, matched-cohort, single-centre study compared pessaries (Cyclogest) versus capsules (Utrogestan, Progeffik) for LPS in hormone replacement treatment-embryo transfer (HRT-ET) cycles. Patients under 50 years old with a triple-layer endometrial thickness of ≥6.5 mm underwent transfer of one or two blastocysts. Serum progesterone concentrations were measured on the day of transfer; patients with concentrations <8.8 ng/ml received a single 'rescue' dose of additional progesterone by subcutaneous injection. RESULTS: In total 2665 HRT-ET cycles were analysed; 663 (24.9%) used pessaries for LPS and 2002 (75.1%) used capsules. Mean serum progesterone concentrations with standard deviations on the day of embryo transfer were significantly higher in the group using MVP pessaries compared with those using capsules (14.5 ± 5.1 versus 13.0 ± 4.8 ng/ml; P = 0.000). The percentage of participants with suboptimal serum progesterone concentrations on the day of embryo transfer (<8.8 ng/ml) was significantly lower in the pessary group than the capsule group (10.3%, 95% confidence interval [CI] 7.9-12.6% versus 17.9%, 95% CI 16.2-19.6%; adjusted odds ratio 0.426, 95% CI 0.290-0.625; P = 0.000). No differences in pregnancy outcome were observed between the groups. CONCLUSIONS: Using MVP pessaries rather than capsules for LPS resulted in significantly fewer patients having suboptimal serum progesterone concentrations on the day of embryo transfer. Consequently, almost 50% fewer patients in the pessary group needed rescue treatment.

Detecting partial premature ovulation during follicular aspiration compromises the quantity, but not the quality, of the oocytes retrieved in stimulated in vitro fertilization (IVF) cycles.

OBJECTIVE: To analyze if partial premature ovulation (PPO) detection during oocyte pick-up (OPU) impairs the quality of the retrieved oocyte cohort. METHODS: The PPO concept refers to the situation when premature ovulation happens only in some of the follicles and it is detected during OPU. This study constitutes a retrospective analysis performed in an infertility clinic (Spain) during 2016-2021 with patients undergoing OPU after controlled ovarian hyperstimulation for an in vitro fertilization (IVF) treatment. Study code: 2110-VLC-091- VG, registered on December 9 2021. Data from women with PPO (n=111) were compared to a matched control sample of cycles without PPO (n=333) at a proportion of 1:3. RESULTS: Cycles were matched for age, body mass index (BMI), treatment year, embryo genetic analysis and stimulation protocol type. The mean numbers of oocytes (6.1 vs. 11.2), mature oocytes (4.7 vs. 8.8), correctly fertilized oocytes (3.6 vs. 6.6) and top-quality blastocysts (0.9 vs. 1.8) were significantly lower in the PPO group than the nonPPO group (p<0.05). However, maturation, fertilization, top-quality blastocyst and pregnancy rates were statistically comparable among groups (p>0.05). CONCLUSIONS: Cycles with PPO have fewer available oocytes and, thus, fewer available embryos for transfer, al though their quality is intact, and still offer chances of pregnancy in these cases. Hence cycle cancellation may not be worth associated money, time and morale losses once PPO is detected.

Duration of oestrogen exposure does not affect reproductive outcome in artificial cycles: a retrospective analysis of more than 7000 hormonal replacement therapy cycles for an embryo transfer.

Introduction: Optimal duration of oestrogen exposure before an embryo transfer in artificial cycles has not been defined yet, as its correlation with reproductive outcome remains controversial. The length of oestrogen treatment before starting luteal phase support varies significantly among patients. Materials and methods: In this study, we conducted a retrospective analysis of a huge database of our own clinical results in artificial cycles in the past five years. The aim of this study was to assess the effect of the length of estrogen exposure on reproductive outcome and to evaluate if there is any optimal duration of estrogen exposure in order to maximize success rates. Results: Differences in pregnancy rates according to oestrogen length, if present, were not clinically relevant. Discussion: Our results suggest that the length of oestrogen exposure (in days) before exogenous progesterone administration do not affect clinical outcomes.

Impacto del confinamiento por COVID-19 en la prescripción de benzodiacepinas / Impact of COVID-19 lockdown on the prescription of benzodiazepines

Objetivo: Evaluar el efecto del confinamiento por COVID-19 sobre la prescripción de benzodiacepinas según edad, sexo y zona básica de salud. Diseño: Estudio observacional longitudinal. Emplazamiento: Atención primaria. Área V de Salud del Principado de Asturias. Participantes: Mayores de 15 años a los que se prescribieron benzodiacepinas entre 2017 y 2020. Mediciones principales: Diferencia de las medias de dosis diaria definida por 1.000 habitantes (DHD) mensual de benzodiacepinas entre el periodo definido como preconfinamiento y el confinamiento. Además, se ajusta la diferencia por edad, sexo y zona básica de salud, así como por la interacción entre ellas. Resultados: La DHD media preconfinamiento fue 131,3 y 139,5 durante el confinamiento; en el análisis crudo, esta diferencia fue estadísticamente significativa (IC 95% 4,1 a 12,1). Se objetivó un aumento de DHD media en el grupo de 60-74 años (IC 95% 2,28 a 21,42) y en el de 90 años o más (IC 95% 21,31 a 40,63), así como en las mujeres (IC 95% 3,51 a 14,59). Finalmente, se observó una disminución de DHD media en las zonas básicas V11 (IC 95% -29 a -0,66) y V14 (IC 95% -54,28 a -25,04). Conclusiones: Determinados subgrupos muestran un cambio en la tendencia de dispensación de benzodiacepinas sin poder atribuirse completamente al confinamiento. Creemos que pueda existir una inercia terapéutica en la prescripción de psicofármacos, según las características biopsicosociales del paciente, que es importante detectar para evitar la medicalización de cuadros psicológicos.(AU)

Objective: To evaluate the effect of COVID-19 lockdown on the prescription of benzodiazepines by gender, age and district health departments. Design: Longitudinal observational study. Location: Primary care. Asturias (Spain) health district V. Participants: People over 15 years of age with filled benzodiazepine prescriptions in between 2017 and 2020. Main measurements: Benzodiazepine DHD (defined daily dose per 1000 habitants) mean difference between the period defined as pre-lockdown and lockdown. Additionally, the difference was adjusted for gender, sex and district health department and also with the interaction among them. Results: DHD mean pre-lockdown was 131.3 and 139.5 in the lockdown; this difference was significant in the global analysis (95% CI: 4.1–12.1). There was an increase in the DHD mean in the 60–74 age group (95% CI: 2.28–21.42), in the group over 90 years old (95% CI: 21.31–40.63) and in women (95% CI: 3.51–14.59). Finally, a decrease in the DHD mean of V11 (95% CI: -29 to -0.66) and V14 (95% CI: -54.28 to -25.04) district health departments was observed.Conclusions: Certain subgroups show a change in the pattern of benzodiazepine prescription without being able to relate this to the lockdown. We believe that there could be some inertia in the prescription of psychiatric medication according to the biopsychosocial characteristics of the patients; it is important to detect this in order to avoid the medicalization of psychological disorders.(AU)

[Impact of COVID-19 lockdown on the prescription of benzodiazepines]. / Impacto del confinamiento por COVID-19 en la prescripción de benzodiacepinas.

OBJECTIVE: To evaluate the effect of COVID-19 lockdown on the prescription of benzodiazepines by gender, age and district health departments. DESIGN: Longitudinal observational study. LOCATION: Primary care. Asturias (Spain) health district V. PARTICIPANTS: People over 15 years of age with filled benzodiazepine prescriptions in between 2017 and 2020. MAIN MEASUREMENTS: Benzodiazepine DHD (defined daily dose per 1000 habitants) mean difference between the period defined as pre-lockdown and lockdown. Additionally, the difference was adjusted for gender, sex and district health department and also with the interaction among them. RESULTS: DHD mean pre-lockdown was 131.3 and 139.5 in the lockdown; this difference was significant in the global analysis (95% CI: 4.1-12.1). There was an increase in the DHD mean in the 60-74 age group (95% CI: 2.28-21.42), in the group over 90 years old (95% CI: 21.31-40.63) and in women (95% CI: 3.51-14.59). Finally, a decrease in the DHD mean of V11 (95% CI: -29 to -0.66) and V14 (95% CI: -54.28 to -25.04) district health departments was observed. CONCLUSIONS: Certain subgroups show a change in the pattern of benzodiazepine prescription without being able to relate this to the lockdown. We believe that there could be some inertia in the prescription of psychiatric medication according to the biopsychosocial characteristics of the patients; it is important to detect this in order to avoid the medicalization of psychological disorders.

Biofilm formation strongly influences the vector transport of triclosan-loaded polyethylene microplastics.

This study aimed at evaluating the influence of biofilm in the role of microplastics (MPs) as vectors of pollutants and their impact on Daphnia magna. To do this, virgin polyethylene MPs, (PE-MPs, 40-48 µm) were exposed for four weeks to wastewater (WW) from influent and effluent to promote biofouling. Then, the exposed PE-MPs were put in contact with triclosan. Finally, the toxicity of TCS-loaded and non-TCS loaded PE-MPs were tested on the survival of D. magna adults for 21 days. Results from metabarcoding analyses indicated that exposure to TCS induced shifts in the bacterial community, selecting potential TCS-degrading bacteria. Results also showed that PE-MPs were ingested by daphnids. The most toxic virgin PE-MPs were those biofouled in the WW effluent. The toxicity of TCS-loaded PE-MPs biofouled in the WW effluent was even higher, reporting mortality in all tested concentrations. These results indicate that biofouling of MPs may modulate the adsorption and subsequent desorption of co-occurring pollutants, hence affecting their potential toxicity towards aquatic organisms. Future studies on realistic environmental plastic impact should include the characterization of biofilms growing on plastic. Since inevitably plastic biofouling occurs over time in nature, it should be taken into account as it may modulate the sorption of co-occurring pollutants.

Recomendaciones de práctica clínica: diagnóstico de osteomielitis en pie diabético / Clinical practice recommendations for the diagnosis of osteomyelitis in the diabetic foot

La osteomielitis (OM) es una complicación de las úlceras en pie diabético que habitualmente es subdiagnosticada y tratada en forma tardía e inadecuada. La demora en el tratamiento de estos pacientes aumenta el riesgo de amputación. En esta revisión, se analiza la bibliografía actual acerca del diagnóstico de OM y se realizan recomendaciones en base a la misma, y a las características de los pacientes, los insumos y las posibilidades en nuestro medio.

Diabetic foot osteomyelitis (OM) is a diabetic foot ulcer complication. Usually, it is misdiagnosed and the treatment is delayed and inadequate. Delaying the treatment of these patients rises the risk of amputation. In this revision, current bibliography about this topic is updated and clinical practice recommendations are done, based on the publications and adapted to the characteristics of our country

Serum progesterone concentrations are reduced in obese women on the day of embryo transfer.

RESEARCH QUESTION: Does serum progesterone concentration vary on the day of embryo transfer according to female body mass index (BMI)? DESIGN: Retrospective analysis including 3210 infertile patients undergoing an embryo transfer in the context of an artificial endometrial preparation cycle with sequential administration of oestrogens and micronized vaginal progesterone (MVP) (400 mg/12 h). Serum progesterone was measured on the day of embryo transfer, 6 ± 2 h after last MVP administration. Serum progesterone concentrations were subdivided into optimal (≥9.2 ng/ml) or suboptimal (<9.2 ng/ml) concentrations, and the cut-off point was defined according to our previous results. The primary objective was the correlation between progesterone concentrations on the day of embryo transfer and patient BMI, as a continuous variable and according to four ranges (underweight: <18.5 kg/m2; normal weight: 18.5-24.9 kg/m2; overweight: 25-29.9 kg/m2; and obesity: ≥30 kg/m2), according to the World Health Organization classification. Secondary objectives included the evaluation of reproductive outcome according to patient BMI and progesterone concentrations on the day of embryo transfer. RESULTS: Mean serum progesterone concentrations and the ratio of patients with progesterone concentrations above the cut-off point of 9.2 ng/ml fell progressively as BMI increased. Overweight and obese patients had lower mean serum progesterone concentrations than underweight and normal weight women (P < 0.001). A trend was observed towards impaired reproductive results in obese patients with suboptimal progesterone concentrations, absent when concentrations were optimal. CONCLUSIONS: Serum progesterone concentrations on the day of embryo transfer in artificial cycles with MPV decrease as BMI increases. It is highly recommended that serum progesterone concentrations are moitored to ensure optimal concentrations and reproductive outcomes.

Role of Mitochondria Transfer in Infertility: A Commentary.

Mitochondria transfer techniques were first designed to prevent the transmission of diseases due to mutations in mtDNA, as these organelles are exclusively transmitted to the offspring by the oocyte. Despite this, given the crucial role of mitochondria in oocyte maturation, fertilization and subsequent embryo development, these approaches have been proposed as new potential strategies to overcome poor oocyte quality in infertile patients. This condition is a very common cause of infertility in patients of advanced maternal age, and patients with previous in vitro fertilization (IVF) attempt failures of oocyte origin. In this context, the enrichment or the replacement of the whole set of the oocyte mitochondria may improve its quality and increase these patients' chances of success after an IVF treatment. In this short review, we will provide a brief overview of the main human studies using heterologous and autologous mitochondria transfer techniques in the reproductive field, focusing on the etiology of the treated patients and the final outcome. Although there is no current clearly superior mitochondria transfer technique, efforts must be made in order to optimize them and bring them into regular clinical practice, giving these patients a chance to achieve a pregnancy with their own oocytes.

Recomendaciones de práctica clínica: diagnóstico de osteomielitis en pie diabético / Clinical practice recommendations for the diagnosis of osteomyelitis in the diabetic foot

Resumen La osteomielitis (OM) es una complicación de las úlceras en pie diabético que habitualmente es subdiagnosticada y tratada en forma tardía e inadecuada. La demora en el tratamiento de estos pacientes aumenta el riesgo de amputación. En esta revisión, se analiza la bibliografía actual acerca del diagnóstico de OM y se realizan recomendaciones en base a la misma, y a las características de los pacientes, los insumos y las posibilidades en nuestro medio.

Abstract Diabetic foot osteomyelitis (OM) is a diabetic foot ulcer complication. Usually, it is misdiagnosed and the treatment is delayed and inadequate. Delaying the treatment of these patients rises the risk of amputation. In this revision, current bibliography about this topic is updated and clinical practice recommendations are done, based on the publications and adapted to the characteristics of our country.

Individualized luteal phase support normalizes live birth rate in women with low progesterone levels on the day of embryo transfer in artificial endometrial preparation cycles.

OBJECTIVE: To analyze the impact on live birth rates (LBRs) of the individualized luteal phase support (termed iLPS) in patients with low serum progesterone (P) levels compared with patients without iLPS. DESIGN: Retrospective cohort study, December 1, 2018, to May 30, 2019. SETTING: Private medical center. PATIENT(S): A total of 2,275 patients checked for serum P on the day of blastocyst transfer were analyzed. During the study period, 1,299 patients showed serum P levels of ≥9.2 ng/mL, whereas 550 showed serum P levels of <9.2 ng/mL and received iLPS. Additionally, a historical group of 426 patients with serum P levels of <9.2 ng/mL but no iLPS were used for comparison. Eligible patients were aged ≤50 years with adequate endometrium morphology after receiving estrogens. Luteal phase support was provided with micronized vaginal P (MVP) to all women. Patients with personalized initiation of exogenous P according to the endometrial receptivity assay test, polyps, fibroids distorting the cavity, or hydrosalpinx were not included in the analysis. INTERVENTION(S): As routine practice since December 2018, patients with low serum P levels received an iLPS with a daily injection of 25 mg of subcutaneous P from the day of embryo transfer (ET) in addition to standard LPS (400 mg of MVP twice a day). MAIN OUTCOME MEASURE(S): Live birth rate. RESULT(S): The LBR was 44.9% in the iLPS cases vs. 45.0% in patients with normal serum P levels (crude odds ratio [OR], 1.0; 95% confidence interval [CI], 0.82-1.22). By regression analysis, low serum P levels did not affect the LBR after adjusting for possible confounders (age, oocyte origin, fresh vs. frozen, day of ET, embryo quality, number of embryos transferred) (adjusted OR, 0.99; 95% CI, 0.79-1.25). Similarly, no differences were observed in other pregnancy outcomes between groups. The LBR was significantly higher in the group of patients who received additional subcutaneous P (iLPS) compared with the historical group with low serum P levels and no iLPS (44.9% vs. 37.3%; OR, 1.37; 95% CI, 1.06-1.78). In the overall population, patients showing P levels of <9.2 ng/mL on the day of ET were slightly younger and had higher body mass index and lower estradiol and P levels during the proliferative phase compared with patients with P levels of ≥9.2 ng/mL. No differences were observed with regard to the time in between the last dose of MVP and the serum P determination. After a multivariable logistic regression analysis, only body mass index and estradiol levels in the proliferative phase reminded statistically significant. Significant differences in the LBR were observed between patients with serum P levels of <9.2 ng/mL without iLPS and patients with serum P levels of ≥9.2 ng/mL when using either own or donated oocytes. CONCLUSION(S): Individualized LPS for patients with low serum P levels produces LBRs similar to those of patients with adequate serum P levels.

What Do We Know about Classical and Non-Classical Progesterone Receptors in the Human Female Reproductive Tract? A Review.

The progesterone hormone regulates the human menstrual cycle, pregnancy, and parturition by its action via the different progesterone receptors and signaling pathways in the female reproductive tract. Progesterone actions can be exerted through classical and non-classical receptors, or even a combination of both. The former are nuclear receptors whose activation leads to transcriptional activity regulation and thus in turn leads to slower but long-lasting responses. The latter are composed of progesterone receptors membrane components (PGRMC) and membrane progestin receptors (mPRs). These receptors rapidly activate the appropriate intracellular signal transduction pathways, and they can subsequently initiate specific cell responses or even modulate genomic cell responses. This review covers our current knowledge on the mechanisms of action and the relevance of classical and non-classical progesterone receptors in female reproductive tissues ranging from the ovary and uterus to the cervix, and it exposes their crucial role in female infertility.

Does Coenzyme Q10 Supplementation Improve Human Oocyte Quality?

Acquiring oocyte competence requires optimal mitochondrial function and adequate ATP levels. In this context, CoQ10 supplementation may improve human oocyte quality and subsequent reproductive performance given its role in ATP synthesis and mitochondrial protection from ROS oxidative damage. In infertility treatments, CoQ10 therapy can be orally supplied to promote a more favorable environment for oocyte development in vivo or by its addition to culture media in an attempt to improve its quality in vitro. Human clinical studies evaluating the impact of CoQ10 on reproductive performance are summarized in this review, although the available data do not clearly prove its ability to improve human oocyte quality. The main objective is to provide readers with a complete overview of this topic's current status as well as the keys for potential future research lines that may help to take this therapy to clinical practice. Indeed, further clinical trials are needed to confirm these results along with molecular studies to evaluate the impact of CoQ10 supplementation on oxidative stress status and mitochondrial function in human gametes.

Mitochondrial enrichment in infertile patients: a review of different mitochondrial replacement therapies.

Poor ovarian responders exhibit a quantitative reduction in their follicular pool, and most cases are also associated with poor oocyte quality due to patient's age, which leads to impaired in vitro fertilisation outcomes. In particular, poor oocyte quality has been related to mitochondrial dysfunction and/or low mitochondrial count as these organelles are crucial in many essential oocyte processes. Therefore, mitochondrial enrichment has been proposed as a potential therapy option in infertile patients to improve oocyte quality and subsequent in vitro fertilisation outcomes. Nowadays, different options are available for mitochondrial enrichment treatments that are encompassed in two main approaches: heterologous and autologous. In the heterologous approach, mitochondria come from an external source, which is an oocyte donor. These techniques include transferring either a portion of the donor's oocyte cytoplasm to the recipient oocyte or nuclear material from the patient to the donor's oocyte. In any case, this approach entails many ethical and safety concerns that mainly arise from the uncertain degree of mitochondrial heteroplasmy deriving from it. Thus the autologous approach is considered a suitable potential tool to improve oocyte quality by overcoming the heteroplasmy issue. Autologous mitochondrial transfer, however, has not yielded as many beneficial outcomes as initially expected. Proposed mitochondrial autologous sources include immature oocytes, granulosa cells, germline stem cells, and adipose-derived stem cells. Presently, it would seem that these autologous techniques do not improve clinical outcomes in human infertile patients. However, further trials still need to be performed to confirm these results. Besides these two main categories, new strategies have arisen for oocyte rejuvenation by improving patient's own mitochondrial function and avoiding the unknown consequences of third-party genetic material. This is the case of antioxidants, which may enhance mitochondrial activity by counteracting and/or preventing oxidative stress damage. Among others, coenzyme-Q10 and melatonin have shown promising results in low-prognosis infertile patients, although further randomised clinical trials are still necessary.

"Hot quadrate lobe spot" sign in chronic superior vena cava obstruction.

We report the case of a 65-year-old male patient who consulted for swelling of the face and neck after having a pacemaker implantated. Contrast-enhanced chest computerized tomography (CT) confirmed a thrombus within the superior vena cava (SVC). Thus, therapy with oral anticoagulants was initiated, which obtained a good clinical response and resolution of symptoms. A follow-up contrast-enhanced CT scan of the chest and abdomen showed a focal, well-delimited, hyperdense area in the IV hepatic segment during the arterial and portal venous phases, which was associated with persistence of the SVC repletion defect and the presence of multiple superficial venous collaterals in the right anterolateral thoraco-abdominal wall. The hepatic image corresponded to the sign of the "hot spot" or "hot quadrate lobe", a hepatic pseudolesion that should not be confused with other focal hypervascular lesions.

Serum Progesterone Profile Across the Mid and Late Luteal Phase in Artificial Cycles Is Associated With Pregnancy Outcome.

Introduction: Recent studies have shown that low serum progesterone levels on the day of embryo transfer (ET) are associated with poorer pregnancy outcome in hormonal replacement therapy cycles. It is of interest to know if serum progesterone levels during late luteal phase (following days after ET) are also related with the chances of ongoing pregnancy. Objective: To evaluate the luteal phase endocrine profile through measurements of serum progesterone and estradiol on days ET+4, ET+7 and ET+11, to test their predictive value in relation to pregnancy outcome. Setting: Private infertility center, Valencia, Spain. Materials and Methods: Prospective cohort study performed between June 2017 and August 2018. Eligible patients were aged between 18-42 years, with a normal uterus, and being transferred 1-2 good quality blastocysts in a frozen ET cycle after an artificial endometrial preparation with estradiol valerate and vaginal micronized progesterone (400 mg/12 hours). Results: A total of 127 patients were included. Mean age = 38.0 ± 3.9 years; BMI = 23.6 ± 3.6 kg/m2; endometrial thickness = 9.1 ± 1.6mm. Overall ongoing pregnancy rate = 47.2% (95%CI:38.3-56.3). Significantly higher levels of serum progesterone were observed on ET+4 (13.6 ± 6.0 vs. 11.1 ± 4.6ng/ml, p = 0.03) and ET+11 (15.7 ± 1.2 vs. 10.3 ± 0.6ng/ml, respectively; p = 0.000) in ongoing pregnancies versus negative ß-hCG (ß-human chorionic gonadotrophin) cases. On ET+7, ongoing pregnancies also had higher serum progesterone levels (14.2 ± 0.9 vs. 11.7 ± 0.8ng/ml, but did not reach statistical significance (p = 0.07). Serum estradiol levels were not related with pregnancy outcome at any moment of the luteal phase (p > 0.05). On days ET+4, +7 and +11, the ROC analysis showed that serum progesterone levels were predictive of ongoing pregnancy, and Pearson's coefficient showed a significant association (p<0.05) of serum ß-hCG levels with serum progesterone. Conclusions: In hormonal replacement therapy cycles, serum progesterone levels across luteal phase days are associated with pregnancy outcome. Ongoing pregnancies were associated with a higher exposure to progesterone in comparison with pregnancy losses or negative ß-hCG. Therefore, serum progesterone might be playing an important role not only during implantation, but also in pregnancy maintenance. It remains unknown if the variability in serum progesterone levels among patients, after receiving the exact same progesterone dose for luteal phase support, is the cause or just a consequence of pregnancy results.

New concepts and difficulties with progesterone supplementation in the luteal phase.

PURPOSE OF REVIEW: Management of the luteal phase (LP) in assisted reproductive cycles has aroused interest in recent years. The reason is that it seems that the individualization of LP support may be necessary, since the concept of 'one size fits all' does not apply to this treatment. RECENT FINDINGS: Studies carried out in hormone replacement therapy cycles (also called artificial cycles) have shown that serum levels of progesterone (P) are related to pregnancy outcomes. This represents a milestone in the management of artificial cycles (AC), because until a few years ago it was believed that serum levels did not really reflect the effectiveness of P, which is why they were neglected. However, it is not as straightforward as it seems, because the interpretation of serum progesterone values will depend on the type of progesterone used and its route of administration. Likewise, the findings observed in AC are not applicable to what occurs in a fresh transfer cycle after ovarian stimulation or an embryo transfer in the context of a natural cycle. SUMMARY: In this manuscript, we will summarize the current situation in LP management.