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Daily transpiration (Td) is crucial for both irrigation water management and increasing crop water productivity. The use of the remote-sensing-based two-source energy balance model (TSEB) has proven to be robust in estimating plant transpiration and evaporation separately for various crops. However, remote sensing models provide instantaneous estimations, and so daily upscaling approaches are needed to estimate daily fluxes. Daily upscaling methodologies have not yet been examined to upscale solely transpiration in woody crops. In this regard, this study aims to evaluate the proper image acquisition time throughout the day and four methodologies used to retrieve Td in almond trees with different production systems and water statuses. Hourly transpiration (Th) was estimated using the TSEB contextual approach (Th–TSEB) with high-resolution imagery five times during two diurnal courses. The tested methodologies were the following: the simulated evaporative fraction variable (EFsim), irradiance (Rs), reference evapotranspiration (ETo), and potential evapotranspiration (ETp). These approaches were first evaluated with in situ sap flow (T–SF) data and were then applied to the Th–TSEB. Daily T–SF showed significant differences among production systems and levels of water stress. The EFsim and ETp methods correlated better with measured T–SF and reduced the underestimation observed using the Rs and ETo methods, especially at noon in the severely water-stressed trees. However, the daily upscaling approaches applied in the TSEB (Td–TSEB) failed to detect differences between production systems. The lack of sensibility of Th–TSEB among production systems poses a challenge when estimating Td in canopies with discontinuous architectural structures. The use of ETp as a reference variable could address this issue as it incorporates various aerodynamic and radiative properties associated with different canopy architectures that influence the daily Th–SF pattern. However, more accurate ETp estimates or more advanced ETp models are needed.

This paper is devoted to the study of optimal release strategies to control vector-borne diseases, such as dengue, Zika, chikungunya and malaria. Two techniques are considered: the sterile insect one (SIT), which consists in releasing sterilized males among wild vectors in order to perturb their reproduction, and the Wolbachia one (presently used mainly for mosquitoes), which consists in releasing vectors, that are infected with a bacterium limiting their vectorial capacity, in order to replace the wild population by one with reduced vectorial capacity. In each case, the time dynamics of the vector population is modeled by a system of ordinary differential equations in which the releases are represented by linear combinations of Dirac measures with positive coefficients determining their intensity. We introduce optimal control problems that we solve numerically using ad-hoc algorithms, based on writing first-order optimality conditions characterizing the best combination of Dirac measures. We then discuss the results obtained, focusing in particular on the complexity and efficiency of optimal controls and comparing the strategies obtained. Mathematical modeling can help testing a great number of scenarios that are potentially interesting in future interventions (even those that are orthogonal to the present strategies) but that would be hard, costly or even impossible to test in the field in present conditions., Competing Interests: Declarations Conflict of interest The authors have no conflict of interest to declare that are relevant to the content of this article., (© 2024. The Author(s).)

Background: The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and thin endometrium (TE), can either originate autonomously or arise as a result from conditions (i.e. endometritis or congenital hypoplasia), or medical interventions (e.g. surgeries, hormonal therapies, uterine curettage or radiotherapy). Affected patients may present an altered or inadequate endometrial lining that hinders embryo implantation and increases the risk of poor pregnancy outcomes and miscarriage. In humans, AS/IUA and EA/TE are mainly treated with surgeries or pharmacotherapy, however the reported efficacy of these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, or tissue engineering have emerged to improve reproductive outcomes., Objective and Rationale: This review comprehensively summarizes the methodologies and outcomes of emerging biotechnologies (cellular, acellular, and bioengineering approaches) to treat human endometrial pathologies. Regenerative therapies derived from human tissues or blood which were studied in preclinical models (in vitro and in vivo) and clinical trials are discussed., Search Methods: A systematic search of full-text articles available in PubMed and Embase was conducted to identify original peer-reviewed studies published in English between January 2000 and September 2023. The search terms included: human, uterus, endometrium, Asherman syndrome, intrauterine adhesions, endometrial atrophy, thin endometrium, endometritis, congenital hypoplasia, curettage, radiotherapy, regenerative therapy, bioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium were included. Additional studies were identified through manual searches., Outcomes: From a total of 4366 records identified, 164 studies (3.8%) were included for systematic review. Due to heterogeneity in the study design and measured outcome parameters in both preclinical and clinical studies, the findings were evaluated qualitatively and quantitatively without meta-analysis. Groups using stem cell-based treatments for endometrial pathologies commonly employed mesenchymal stem cells (MSCs) derived from the human bone marrow or umbilical cord. Alternatively, acellular therapies based on platelet-rich plasma (PRP) or extracellular vesicles are gaining popularity. These are accompanied by the emergence of bioengineering strategies based on extracellular matrix (ECM)-derived hydrogels or synthetic biosimilars that sustain local delivery of cells and growth factors, reporting promising results. Combined therapies that target multiple aspects of tissue repair and regeneration remain in preclinical testing but have shown translational value. This review highlights the myriad of therapeutic material sources, administration methods, and carriers that have been tested., Wider Implications: Therapies that promote endometrial proliferation, vascular development, and tissue repair may help restore endometrial function and, ultimately, fertility. Based on the existing evidence, cost, accessibility, and availability of the therapies, we propose the development of triple-hit regenerative strategies, potentially combining high-yield MSCs (e.g. from bone marrow or umbilical cord) with acellular treatments (PRP), possibly integrated in ECM hydrogels. Advances in biotechnologies together with insights from preclinical models will pave the way for developing personalized treatment regimens for patients with infertility-causing endometrial disorders such as AS/IUA, EA/TE, and endometritis., Registration Number: https://osf.io/th8yf/., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Previous studies have found inconsistent associations between heavy metals and metalloids (cadmium, lead, mercury, and arsenic), and reproductive outcomes. The biofluid concentrations of ten non-essential trace elements (Hg, Pb, As, Ba, Sr, Rb, Cs, Sn, Ni, and Co) were evaluated in 51 Spanish women undergoing ICSI, PGT-A, and SET/FET. Nine out of ten non-essential elements were detectable in follicular fluid, whole blood, and urine collected the day of vaginal oocyte retrieval (VOR) and the day of embryo transfer and then analyzed by ICP-MS or Tricell DMA-80 for mercury. Elevated mercury and strontium concentrations in follicular fluid were associated with poor ovarian response and preimplantation outcomes. Worst preimplantation outcomes were also identified in women with elevated whole-blood strontium or mercury, urinary arsenic, barium, and tin the day of VOR. High concentrations of urinary rubidium on VOR day were linked with enhanced fertilization and blastocyst development. Excessive titanium in whole blood was associated with lower odds of implantation, clinical pregnancy, and achieving a live birth in a given IVF cycle. Excessive urinary arsenic on the day of embryo transfer was associated with lower odds of live birth. Although these preliminary results need to be confirmed in larger populations, distinguishing organic and inorganic element forms, our findings show that some non-essential elements have a detrimental impact on human IVF outcomes.

Background: Recently, the potential detrimental effect that the duration of storage time may have on vitrified samples has raised some concerns, especially when some studies found an association between cryostorage length and decreased clinical results., Objective: This study aimed to evaluate the effects of the storage time length of day-5 vitrified blastocysts in 2 study groups: freeze-all cycles and nonelective frozen embryo transfers., Study Design: This was a retrospective study that included 58,001 vitrified/warmed day-5 blastocysts from 2 different populations, according to the reason for frozen embryo transfer. Elective frozen embryo transfer comprised freeze-all cycles (N=16,615 blastocysts and 16,615 patients) in which only single embryo transfers and only the first frozen embryo transfer were included. The nonelective frozen embryo transfer group included 41,386 embryos from 25,571 patients where frozen embryo transfer took place using supernumerary embryos after fresh embryo transfer. All the possible frozen embryo transfers were included. Both single embryo transfer and double embryo transfers were included. Donor and autologous oocytes were used. The period covered by this study was 11 years. The blastocyst sample was clustered into deciles, which provided specific storage duration categories. The main outcome was the live birth rate, and secondary outcomes were embryo survival, miscarriage, and clinical and ongoing pregnancy rates according to storage duration. The impact of storage time was assessed by univariable analyses in both groups. The comparison was made between each decile and the last one. A multivariable logistic regression analysis was conducted, including the variables with significant association found in the univariate analysis. Student t test and chi-square tests, or an analysis of variance, were used wherever appropriate. P<.05 was considered statistically significant., Results: There were statistical differences in baseline characteristics of patients included in the study groups. Storage durations ranged from ≤0.67 to ≥4.34 and from ≤1.8 to ≥34.81 months in freeze-all and nonelective frozen embryo transfer, respectively. Embryo survival did not show statistical differences across the categories of storage time in freeze-all and nonelective frozen embryo transfer groups. Statistical differences were found for the live birth rate across some, but not all, the subgroups of storage duration. The multivariable analysis showed no association between storage time and the live birth rate in both groups (nonsignificant). Blastocyst quality, body mass index, number of retrieved oocytes, endometrial preparation, male factor, and uterine factor were related to the drop in the live birth rate in the freeze-all group (P<.05). In the nonelective frozen embryo transfer group, the variables that showed significant association with the live birth rate were age at retrieval and frozen embryo transfer, type of frozen embryo transfer (single embryo transfer or double embryo transfers), number of retrieved oocytes, body mass index, endometrial preparation, origin of sperm sample, and female factor., Conclusion: This large study demonstrated no association between storage time and clinical outcome. Other variables, such as the patient's age, embryo quality, body mass index, and etiology, are somewhat responsible for impacting the outcome. This provides evidence for the safety of embryo vitrification, even after long storage periods. This is reassuring for both in vitro fertilization practitioners and patients undergoing frozen embryo transfer of either elective or nonelective embryos., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mosquito species, including the Asian tiger mosquito, can transmit disease-causing pathogens such as dengue, Zika, and chikungunya, with their population dynamics influenced by a variety of factors including climate shifts, human activity, and local environmental conditions. Understanding these dynamics is vital for effective control measures. Our study, conducted in Jardí Botanic Marimurtra from May to November 2021, monitored Ae. albopictus activity using BG-Traps and investigated larval control effects. We employed Generalized Linear Mixed Models to analyze variables like weather, human presence, and larvicidal control on adult mosquito abundance. Adults of Ae. albopictus exhibited a seasonal pattern influenced by temperature but with bimodal peaks linked to cumulative rainfall. Proximity to stagnant water and visitor influx directly affected mosquito captures. Additionally, the effectiveness of larvicide treatments depended on interactions between preceding rainfall levels and treatment timing. Our research emphasizes the significance of studying vector ecology at local scales to enhance the efficacy of control programs and address the escalating burden of vector-borne diseases. Considering the impacts of extreme weather events and climate shifts is essential for the development of robust vector control strategies. Furthermore, our distinct findings serve as a prime illustration of utilizing statistical modeling to gain mechanistic insights into ecological patterns and processes.

Essential trace elements are micronutrients whose deficiency has been associated with altered fertility and/or adverse pregnancy outcomes, while surplus may be toxic. The concentrations of eight essential trace elements were measured using inductively coupled mass spectrometry (ICP-MS) and assessed with respect to clinical in vitro fertilization (IVF) outcomes in a population of 51 women undergoing IVF with intracytoplasmic sperm injection (ICSI), pre-implantation genetic screening for aneuploidy (PGT-A), and single frozen euploid embryo transfer (SET/FET). Specifically, copper (Cu), zinc (Zn), molybdenum, selenium, lithium, iron, chromium, and manganese were quantified in follicular fluid and whole blood collected the day of vaginal oocyte retrieval (VOR) and in urine collected the day of VOR and embryo transfer. We found that the whole blood Cu/Zn ratio was significantly associated with superior responses to ovarian stimulation. Conversely, the whole blood zinc and selenium concentrations were significantly associated with poor ovarian response outcomes. Higher levels of whole blood zinc and selenium, urinary selenium, lithium, and iron had significant negative associations with embryologic outcomes following IVF. Regarding clinical IVF outcomes, higher urinary molybdenum concentrations the day of VOR were associated with significantly lower odds of implantation and live birth, while higher urinary Cu/Mo ratios on the day of VOR were associated with significantly higher odds of implantation, clinical pregnancy, and live birth. Our results suggest that essential trace element levels may directly influence the IVF outcomes of Spanish patients, with selenium and molybdenum exerting negative effects and copper-related ratios exerting positive effects. Additional studies are warranted to confirm these relationships in other human populations.

We propose a two stages mosquito egg-larvae model with seasonality as a simplification of a four stages one. For the simplified model we characterize the dynamics in terms of the vectorial reproduction number, [Formula: see text], obtaining extinction if [Formula: see text] and convergence to a unique positive periodic orbit if [Formula: see text]. We illustrate each case with an example, by providing general conditions on the periodic coefficients for its occurrence. These examples are further developed using numerical simulations where the periodic parameters satisfy the conditions obtained. In the [Formula: see text] case, real climatic data is used for inferring the parameter behaviour. For the four stage system, using alternative oviposition rate functions, we present a result which generalizes others given for models with delays and even with diffusion to the case in which competition between the larvae is introduced. The analytical study of our initial four stages system when [Formula: see text] remains open, since we were not able to prove that in this case the system is dissipative., (© 2023. The Author(s).)

Research Question: What is the population undergoing the ROPA (Reception of Oocytes from Partner) method and what are the outcomes of the technique?, Design: Case series of all ROPA treatments carried out between 2011 and 2020 in 18 fertility clinics in Spain. Demographic characteristics, cycle features, laboratory and clinical outcomes, and the intentions regarding the disposition of surplus embryos were analysed., Results: Donor patients were on average 3.5 years younger than recipients (P = 0.001). No significant differences were found in body mass index or anti-Müllerian hormone. In 13% of cases, fertility issues were found: poor ovarian reserve (6.8%); endometriosis (2.9%); and polycystic ovary syndrome (2.2%). Including cases of advanced age (38 years old or older), more than one-half of couples (53.6%) had some condition that could affect fertility. Mean number of mature oocytes per cycle was 10 (+/- 5.7), and fertilization rate was 74.5% (+/- 18.8). Mean number of viable embryos was 3.2 (+/- 1.5). Surplus embryos were cryopreserved in 50.4% of cycles. Outcomes after embryo transfers from ROPA, and subsequent frozen cycles were as follows: positive pregnancy test (61.0%), clinical pregnancy (54.1%) and miscarriage rate (16.1%). Other outcomes were live birth rate per embryo transfer (44.7%); multiple pregnancy rate (5.4%); per cumulative ROPA cycle (48.6%); and per couple (61.6%)., Conclusion: The outcomes of the ROPA method are reassuring. About one-half of the ROPA cycles resulted in a live birth and one-quarter of the cycles had surplus embryos after achieving a live birth. Main neonatal outcomes were also reassuring., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate female couples' reproductive choices, the importance given to genetics and pregnancy and their expectations regarding mother-child relationship., Methods: Observational study based on an anonymous survey applied to 217 patients during 2021. The survey was given to female couples under reproductive treatment in a private fertility clinic. The outcomes were divided into 3 main groups: the choice of their reproductive treatment, motherhood and biological links, and their plans for future reproductive treatments., Results: Most patients found it easy to choose their treatments and roles. The choice was mainly driven by success rates, costs, and simplicity, except for ROPA for which sharing biological motherhood was the main reason. Most couples consider genetics and pregnancy important but, in the end, they believe they will have a similar connection to their child, regardless of the role played. In the future, some couples consider doing the same treatment while others consider inverting roles., Conclusions: Most female couples have no difficulty when it comes to choosing a reproductive treatment or role to play, mainly based on costs, success rates and the possibility of sharing biological motherhood with the ROPA method. These patients give great importance to genetics and pregnancy, but they expect a similar connection to their child regardless of the type of treatment and the roles played.

Endometrial receptivity and its management in assisted reproduction is now a significant focus of research interest. Endometrial receptivity tests, which analyze different panels of gene expression, are usually offered in fertility clinics to determine the women's individual 'window of implantation', providing a personalized timing for embryo transfer. However, there are still no definite indications on whether its inclusion in the study of the infertile couple or the study of patients with repeated implantation failure is essential., (© 2023 The Authors.)

Study Question: For a woman with infertility and overweight/obesity, can infertility treatment be postponed to first promote weight loss?, Summary Answer: Advice regarding a delay in IVF treatment to optimize female weight should consider female age, particularly in women over 38 years for whom only substantial weight loss in a short period of time (3 months) seems to provide any benefit., What Is Known Already: Body weight excess and advanced age are both common findings in infertile patients, creating the dilemma of whether to promote weight loss first or proceed to fertility treatment immediately. Despite their known impact on fertility, studies assessing the combined effect of female age and BMI on cumulative live birth rates (CLBRs) are still scarce and conflicting., Study Design, Size, Duration: We performed a multicentre retrospective cohort study including 14 213 patients undergoing their first IVF/ICSI cycle with autologous oocytes and subsequent embryo transfers, between January 2013 and February 2018 in 18 centres of a multinational private fertility clinic. BMI was subdivided into the following subgroups: underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obesity (≥30.0 kg/m2)., Participants/materials, Setting, Methods: The primary outcome was CLBR. The secondary outcome was time to pregnancy. To assess the influence of female age and BMI on CLBR, two multivariable regression models were developed with BMI being added in the models as either an ordinal categorical variable (Model 1) or a continuous variable (Model 2) using the best-fitting fractional polynomials. CLBR was estimated over 1-year periods (Model 1) and shorter timeframes of 3 months (Model 2). We then compared the predicted CLBRs according to BMI and age., Main Results and the Role of Chance: When compared to normal weight, CLBRs were lower in women who were overweight (adjusted odds ratio (aOR) 0.86, 95% CI 0.77-0.96) and obese (aOR 0.74, 95% CI 0.62-0.87). A reduction of BMI within 1 year, from obesity to overweight or overweight to normal weight would be potentially beneficial up to 35 years old, while only a substantial reduction (i.e. from obesity to normal BMI) would be potentially beneficial in women aged 36-38 years. Above 38 years of age, even considerable weight loss did not compensate for the effect of age over a 1-year span but may be beneficial in shorter time frames. In a timeframe of 3 months, there is a potential benefit in CLBR if there is a loss of 1 kg/m2 in BMI for women up to 33.25 years and 2 kg/m2 in women aged 33.50-35.50 years. Older women would require more challenging weight loss to achieve clinical benefit, specifically 3 kg/m2 in women aged 35.75-37.25 years old, 4 kg/m2 in women aged 37.50-39.00 years old, and 5 kg/m2 or more in women over 39.25 years old., Limitations, Reasons for Caution: This study is limited by its retrospective design and lower number of women in the extreme BMI categories. The actual effect of individual weight loss on patient outcomes was also not evaluated, as this was a retrospective interpatient comparison to estimate the combined effect of weight loss and ageing in a fixed period on CLBR., Wider Implications of the Findings: Our findings suggest that there is potential benefit in weight loss strategies within 1 year prior to ART, particularly in women under 35 years with BMI ≥25 kg/m2. For those over 35 years of age, weight loss should be considerable or occur in a shorter timeframe to avoid the negative effect of advancing female age on CLBR. A tailored approach for weight loss, according to age, might be the best course of action., Study Funding/competing Interest(s): No specific funding was obtained for this study. All authors have no conflicts to declare., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Preoperative anaemia is associated with poor outcomes in surgical patients, but the preoperative haemoglobin cut-off that determines lower morbidity in total knee arthroplasty (TKA) and total hip arthroplasty (THA) is not well established., Methods: Planned secondary analysis of data collected during a multicentre cohort study of patients undergoing THA and TKA in 131 Spanish hospitals during a single 2-month recruitment period. Anaemia was defined as haemoglobin <12 g dl -1 for females and < 13 g dl -1 for males. The primary outcome was the number of patients with 30-day in-hospital postoperative complications according to European Perioperative Clinical Outcome definitions and specific surgical TKA and THA complications. Secondary outcomes included the number of patients with 30-day moderate-to-severe complications, red blood cell transfusion, mortality, and length of hospital stay. Binary logistic regression models were constructed to assess association between preoperative Hb concentrations and postoperative complications, and variables significantly associated with the outcome were included in the multivariate model. The study sample was divided into 11 groups based on preoperative Hb values in an effort to identify the threshold at which increased postoperative complications occurred., Results: A total of 6099 patients were included in the analysis (3818 THA and 2281 TKA), of whom 8.8% were anaemic. Patients with preoperative anaemia were more likely to suffer overall complications (111/539, 20.6% vs. 563/5560, 10.1%, p < .001) and moderate-to-severe complications (67/539, 12.4% vs. 284/5560, 5.1%, p < .001). Multivariable analysis showed preoperative haemoglobin ≥14 g dl -1 was associated with fewer postoperative complications., Conclusion: Preoperative haemoglobin ≥14 g dl -1 is associated with a lower risk of postoperative complications in patients undergoing primary TKA and THA., (© 2023 Acta Anaesthesiologica Scandinavica Foundation.)

Thrombophilia is a group of inherited or acquired coagulation disorders that have been associated with reproductive failure. However, there are still no clear recommendations on whether its inclusion in the initial study of the infertile couple or patients with recurrent implantation failure is necessary. In this discussion paper, based on a SWOT (strengths, weaknesses, opportunities, threats) analysis, the different aspects of the repercussions of thrombophilia screening and treatment in reproduction are evaluated. To avoid possible subjectivity in the analysis and results of this study, researchers followed Oxford criteria for the evaluation of evidence. The results from the evaluation of the reviewed bibliography seem to indicate that, pending new evidence, it would be advisable not to include thrombophilia screening in the initial baseline study of the infertile couple. There is no evidence to support a clear association between thrombophilia and implantation failure or infertility. Thrombophilia testing in this setting may increase cost, with minimal potential benefit and lead to inappropriate use of anticoagulants with possible deleterious adverse effects. Future well-designed studies are needed to assess the possible benefit of anticoagulant therapy in infertile thrombophilic patients with implantation failure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

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/m 2 ; normal weight: 18.5-24.9 kg/m 2 ; overweight: 25-29.9 kg/m 2 ; and obesity: ≥30 kg/m 2 ), 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., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: To compare reproductive outcomes of the ROPA method (reception of oocytes from partner) to IVF with autologous oocytes. To study the impact of the absence of a genetic link between the embryo and its recipient in reproductive outcomes., Methods: Retrospective multicentric cohort study performed from January 2011 to December 2020 in 18 fertility clinics in Spain. A total of 99 ROPA (73 couples) and 2929 non-ROPA cycles (2334 couples or single patients) of women younger than 38 years old with no known female fertility disorder were included. Clinical outcomes were compared between both groups and included positive pregnancy test, clinical pregnancy, miscarriage, ectopic pregnancy, pre-term birth, live birth, weeks of gestation at birth, and newborn weight at birth., Results: No differences were found between groups in clinical outcomes. The total clinical pregnancy rates per embryo transfer were 57% and 50.2% (p = 0.15) and the live-birth rates were 46.1% and 40.9% (p = 0.14) for the ROPA and non-ROPA groups, respectively. When adjusted to age and BMI of donors and recipients, there were also no differences in live-birth rates between both groups. The cumulative live-birth rate per ROPA cycle was 73.7% and the cumulative live-birth rate per couple was 78.3%., Conclusion: Clinical outcomes following the ROPA method and IVF with autologous oocytes were found to be similar. These findings suggest no impact of the absence of genetic ties between the embryo and the uterus on reproductive treatments' outcomes. Data regarding the outcomes of the ROPA method are reassuring., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: To summarize recent findings related to the risk of miscarriage in women with elevated BMI undergoing IVF, and the mechanisms involved in said risk., Recent Findings: Miscarriage rates are increased in overweight and obese women in both natural and assisted reproduction. Oocyte and embryo quality assessed according to classic morphological static parameters does not seem to be affected by excessive female body weight. Despite the initial lack of consensus between studies regarding embryo morphokinetics in obese women, blastocyst formation and quality have recently been shown to be similar across BMI groups, even in the case of euploid embryos. However, some metabolomic differences have been described in oocytes and embryos from obese women, thus pointing to a functional alteration. In women with elevated BMI, the percentage of aneuploid embryos is similar to that of normal weight women, and rates of miscarriage are higher, despite the transfer of euploid embryos. Therefore, the origin of the increased pregnancy loss rate after IVF in these women may be related to metabolomic, epigenetic or mitochondrial oocyte and embryo disturbances, or to the abnormal endocrine, metabolic and inflammatory uterine environment induced by obesity, which seems to be also responsible for other numerous complications during pregnancy and the in-utero fetal programming of postnatal diseases. A displacement of the window of implantation in obese women undergoing artificial endometrial preparation has recently been described and may be related to the poorer embryo implantation rates and increased risk of miscarriage observed following fresh and frozen embryo transfers with autologous oocytes, and with donated ova in recipients with extremely high BMI., Summary: Female obesity is related to poorer outcome in natural and assisted conception, including an increased risk of miscarriage. Embryo morphology, assessed by conventional methods or by morphokinetics, does not seem to be affected by excess weight, with similar blastocyst formation and quality than normal weight women reported in IVF cycles. Embryo aneuploidy is not increased, and higher miscarriages rates are seen after euploid embryo transfer in obese women. Disturbances of the uterus or its environment induced by female obesity seem to be the most likely cause of the increased risk of miscarriage, although metabolomic, epigenetic or mitochondrial oocyte and embryo dysfunction cannot be ruled out as cannot congenital anomalies. In the context of all the above, weight reduction before pregnancy should be advised in obese women trying to become pregnant., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Recently, a technique of assisted reproduction was developed to allow lesbian women to share biological motherhood of their offspring - the ROPA method (in Spanish - Recepción de Ovocitos de Pareja; in English - Reception of Partner's Oocytes), also known as lesbian shared in vitro fertilization. One mother provides the oocytes (genetic mother) and the other receives the embryo and gets pregnant (gestational mother). As for most issues related to medically assisted reproduction, this technique raises a lot of ethical questions in respect to patients, future offspring, gametes, and embryos. Furthermore, the fact that it is directed to homosexual women poses its own issues, both biological and social in nature. This is a state-of-the-art review of the main ethical dilemmas related to this technique, primarily focusing on the basic principles of bioethics, but also specific concerns directly related to this kind of treatments., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Study Question: Does the embryo cleavage pattern and rate of blastocyst formation differ between normal weight and obese women undergoing IVF?, Summary Answer: Embryo morphokinetic development, final blastocyst formation rate and blastocyst morphology do not differ between obese and normal weight women., What Is Known Already: Female obesity has been related to impaired IVF outcomes. Although the mechanisms responsible for this detrimental effect are thought to include impaired oocyte and embryo quality and reduced endometrial receptivity, they are yet to be confirmed. Embryo quality has been commonly assessed using static morphological criteria. Only three studies have analysed the progress of embryos up to the blastocyst stage in women with elevated BMI, but they have used small samples of patients or have obtained contradictory results., Study Design, Size, Duration: This retrospective, cohort study, was performed from January 2016 to May 2020. A total of 3316 ICSI cycles from 2822 women were included, of which 1251 cycles were part of a preimplantation genetic testing programme. In total, 17 848 embryos were analysed., Participants/materials, Setting, Methods: This study reports on the IVF cycles of infertile women, with a known BMI, who underwent ICSI and whose embryos were grown until the fifth/sixth day of development in a time-lapse system. Patients were grouped as follows. Underweight was defined as a BMI <18.5 kg/m2; normal weight was a BMI of 18.5-24.9 kg/m2; overweight was a BMI of 25-29.9 kg/m2; and obesity was a BMI of ≥30 kg/m2. Embryo development was assessed on an external computer with analysis software., Main Results and the Role of Chance: Despite an initial slower pattern of embryo development, the blastocyst formation rate on day 5 or on day 5 plus day 6 did not differ in obese women with respect to the other three BMI groups. Moreover, based on the evaluation of inner cell mass and the trophectoderm on both days of blastocyst development, embryo quality was similar across the BMI groups, as were the pattern of development and arrest up to blastocyst formation and the distribution of the categories of full, expanded and hatching blastocysts., Limitations, Reasons for Caution: Limitations include the retrospective analysis of data, the use of BMI as the only parameter to define normal/abnormal female body weight, and the lack of complete information about clinical outcomes., Wider Implications of the Findings: Blastocyst formation and embryo morphokinetics are not affected by female obesity, and the poorer IVF outcomes described for such women are probably due to deficient endometrial receptivity. The role of endometrial progesterone exposure on the day of embryo transfer should be analysed in future studies as a possible determining factor., Study Funding/competing Interest(s): No external funding was used and there are no competing interests., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Our aim was to determine prospectively whether increased body mass index (BMI) affects endometrial receptivity through displacement of the window of implantation (dWOI) using the endometrial receptivity analysis (ERA), and whether this effect is BMI-dependent. We recruited a population of 170 infertile women with a normal uterus and no clinical history of recurrent miscarriage or implantation failure. These women were divided into four groups according to BMI: normal weight (18.5-24.9 kg/m 2 ; n = 44), overweight (25-29.9 kg/m 2 ; n = 29), class I obese (30.0-34.9 kg/m 2 ; n = 54), and class II and III obese (> 35 kg/m 2 ; n = 43). We also assigned the patients to one of two larger BMI cohorts: non-obese (normal weight and overweight; n = 73) and obese (class I, II, and III obese; n = 97). We compared analytical and clinical data and dWOI in these categories, finding significant metabolic differences in glycemia, TSH, insulin, HDL cholesterol, LDL cholesterol, triglycerides, and systolic and diastolic blood pressure among the different BMI groups. One-day dWOI increased significantly with BMI, and significant differences were observed in the non-obese versus obese categories (9.7% vs 25.3 %, respectively (p = 0.02)). dWOI was most pronounced in patients with class II-III obesity. In addition, displacement was longer as BMI increased since ERA revealed a higher proportion of displacements of 1 day than of 12 h and showed they were predominantly pre-receptive. In conclusion, obesity has a negative effect on endometrial receptivity through delaying of the WOI, which increases in function of BMI as well as the metabolic disturbances of the patient., (© 2021. Society for Reproductive Investigation.)

Objective: To determine whether female body mass index (BMI) is associated with an increased risk of miscarriage after euploid embryo transfer., Design: A retrospective, observational, multicenter cohort study., Setting: University-affiliated in vitro fertilization center., Patient(s): In this study, 3,480 cycles of in vitro fertilization with preimplantation genetic testing for aneuploidy (PGT-A) in the blastocyst stage and euploid embryo transfer were divided into four groups according to patient BMI., Intervention(s): In vitro fertilization with PGT-A., Main Outcome Measure(s): The primary outcome was the miscarriage rate, which included both biochemical and clinical miscarriages. Secondary outcomes were implantation, pregnancy, clinical pregnancy, and live birth rates., Result(s): Cycles were divided into four groups according to BMI (kg/m 2 ): underweight (<18.5; n = 155), normal weight (18.5-24.9; n = 2,549), overweight (25-29.9; n = 591), and obese (≥30; n = 185). The number of PGT-A cycles per patient was similar in the four groups. Fertilization rate, day of embryo biopsy, technique of chromosomal analysis, number of euploid embryos, number of transferred embryos, and method of endometrial preparation for embryo transfer were similar in the four BMI groups. Miscarriage rates were significantly higher in women with obesity compared to women with normal weight, mainly due to a significant increase in the clinical miscarriage rates. Live birth rates also were lower in women with obesity. Obesity in women and day 6 trophectoderm biopsy were found to influence the reduced live birth rate., Conclusion(s): Women with obesity experience a higher rate of miscarriage after euploid embryo transfer than women with a normal weight, suggesting that other mechanisms than aneuploidy are responsible for this outcome., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Chronic endometritis is a pathology often associated with reproductive failure, but there are still no clear recommendations on whether its inclusion in the initial study of infertile couples is necessary. In this discussion paper, based on a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis, the different aspects of the repercussions of chronic endometritis in fertility are evaluated. To avoid possible subjectivity in the analysis and results of this study, the researchers followed the Oxford criteria for the evaluation of evidence. The results from the evaluation of the reviewed literature seem to indicate that, pending new evidence, it would be advisable not to include chronic endometritis in the initial baseline study before assisted reproduction in order not to delay other assisted reproduction treatments. However, it would be advisable in cases of repetitive implantation failure and pregnancy loss after having undergone IVF with viable embryos and before continuing with costly reproductive processes, since results could be improved. The development of randomized studies assessing the impact of antibiotic treatment as a possible therapeutic option in infertile women with chronic endometritis, as well as the possible impact on endometrial microbiota and receptivity/implantation, would allow for the establishment of more precise clinical guidelines in this regard., (Copyright © 2021 Reproductive Healthcare Ltd. All rights reserved.)

Study Question: Is there a serum progesterone (P) threshold on the day of embryo transfer (ET) in artificial endometrium preparation cycles below which the chances of ongoing pregnancy are reduced?, Summary Answer: Serum P levels <8.8 ng/ml on the day of ET lower ongoing pregnancy rate (OPR) in both own or donated oocyte cycles., What Is Known Already: We previously found that serum P levels <9.2 ng/ml on the day of ET significantly decrease OPR in a sample of 211 oocyte donation recipients. Here, we assessed whether these results are applicable to all infertile patients under an artificial endometrial preparation cycle, regardless of the oocyte origin., Study Design, Size, Duration: This prospective cohort study was performed between September 2017 and November 2018 and enrolled 1205 patients scheduled for ET after an artificial endometrial preparation cycle with estradiol valerate and micronized vaginal P (MVP, 400 mg twice daily)., Participants/materials, Setting, Methods: Patients ≤50 years old with a triple-layer endometrium ≥6.5 mm underwent transfer of one or two blastocysts. A total of 1150 patients treated with own oocytes without preimplantation genetic testing for aneuploidies (PGT-A) (n = 184), own oocytes with PGT-A (n = 308) or donated oocytes (n = 658) were analyzed. The primary endpoint was the OPR beyond pregnancy week 12 based on serum P levels measured immediately before ET., Main Results and the Role of Chance: Women with serum P levels <8.8 ng/ml (30th percentile) had a significantly lower OPR (36.6% vs 54.4%) and live birth rate (35.5% vs 52.0%) than the rest of the patients. Multivariate logistic regression showed that serum P < 8.8 ng/ml was an independent factor influencing OPR in the overall population and in the three treatment groups. A significant negative correlation was observed between serum P levels and BMI, weight and time between the last P dose and blood tests and a positive correlation was found with age, height and number of days on HRT. Multivariate logistic regression showed that only body weight was an independent factor for presenting serum P levels <8.8 ng/ml. Obstetrical and perinatal outcomes did not differ in patients with ongoing pregnancy regardless of serum P levels being above/below 8.8 ng/ml., Limitations, Reasons for Caution: Only women with MVP were included. Extrapolation to other P administration forms needs to be validated., Wider Implications of the Findings: This study identified the threshold of serum P as 8.8 ng/ml on the day of ET for artificial endometrial preparation cycles necessary to optimize outcomes, in cycles with own or donated oocytes. One-third of patients receiving MVP show inadequate levels of serum P that, in turn, impact the success of the ART cycle. Monitoring P levels in the mid-luteal phase is recommended when using MVP to adjust the doses according to the needs of the patient., Study Funding/competing Interest(s): None., Trial Registration Number: NCT03272412., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Intracytroplasmatic sperm injection (ICSI) is a common procedure used to improve reproductive results, even among couples without male factor infertility. However, the evidence available is still uncertain on the possible advantages and deficiencies that this procedure may have in patients with no formal indication for ICSI., Methods: A SWOT (strengths, weaknesses, opportunities, threats) analysis examines the possible advantages and deficiencies of performing ICSI in these patients with no formal indication., Results: The evidence suggests that ICSI is not justified for non-male factor infertile couples requiring in vitro conception. One of the major strengths associated to the procedure is the virtual elimination of cases further complicated by total fertilization failure and a combination between IVF and ICSI on sibling oocytes has been advised in the literature. Greater technical difficulties, higher costs and performing an unnecessary invasive technique in some cases represent some of the weaknesses of the procedure, and questions regarding safety issues should not be ruled out., Conclusion: Despite the widespread use of ICSI in patients without a formal diagnosis of male factor infertility, evidence demonstrating its effectiveness in this population is still lacking. Additional large and well-designed randomized controlled trials are needed to clarify definitive indications for ICSI in non-male factor infertility.

Objective: To investigate whether the morphodynamic characterization of a euploid blastocyst's development allows a higher prediction of a live birth after single-embryo-transfer (SET)., Design: Observational cohort study conducted in two phases: training and validation., Setting: Private in vitro fertilization centers., Patient(s): Euploid blastocysts: 511 and 319 first vitrified-warmed SETs from 868 and 546 patients undergoing preimplantation genetic testing for aneuploidies (PGT-A) in the training and validation phase, respectively., Intervention(s): Data collected from time of polar body extrusion to time of starting blastulation, and trophectoderm and inner-cell-mass static morphology in all embryos cultured in a specific time-lapse incubator with a continuous medium. Logistic regressions conducted to outline the variables showing a statistically significant association with live birth. In the validation phase, these variables were tested in an independent data set., Main Outcome Measure(s): Live births per SET., Result(s): The average live birth rate (LBR) in the training set was 40% (N = 207/511). Only time of morulation (tM) and trophectoderm quality were outlined as putative predictors of live birth at two IVF centers. In the validation set, the euploid blastocysts characterized by tM <80 hours and high-quality trophectoderm resulted in a LBR of 55.2% (n = 37/67), while those with tM ≥ 80 hours and a low-quality trophectoderm resulted in a LBR of 25.5% (N = 13/51)., Conclusion(s): Time of morulation and trophectoderm quality are better predictors of a euploid blastocyst's reproductive competence. Our evidence was reproducible across different centers under specific culture conditions. These data support the crucial role of morulation for embryo development, a stage that involves massive morphologic, cellular, and molecular changes and deserves more investigation., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Second-generation preimplantation genetic testing for aneuploidy (PGT-A 2.0) in patients with an unfavourable reproductive and IVF prognosis is becoming common practice, with the aim of improving reproductive outcomes. However, there is still no clear evidence on the possible advantages and drawbacks with regard to this procedure. In this discussion paper, based on a SWOT (strengths, weaknesses, opportunities, threats) analysis, the different aspects of this strategy are evaluated. Current evidence suggests that PGT-A 2.0 should not at present have an indiscriminate application, but it might be indicated in cases in which the risk of aneuploidy is increased., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Does ovarian stimulation for oocyte vitrification affect disease-free survival and overall survival rates in women with early breast cancer?, Design: This cohort study included 259 patients with early breast cancer; 148 patients underwent ovarian stimulation, whereas 111 patients did not. Patients were treated between January 2008 and December 2016. To calculate the disease-free survival time and overall survival rate, the time of definitive surgery was defined as the starting point. The follow-up was conducted up to 5 years., Results: Exposed and non-exposed groups were comparable in tumour, node and metastases classification, Nottingham grade, hormonal receptor status, tumour molecular phenotype, histology and pathology stage. The exposed group was younger than the non-exposed. Recurrences occurred in 9/148 women (6.1%) in the exposed group and 15/111 women (13.5%) in the non-exposed group, with no significant difference. The mean disease-free survival time was 63.9 months (95% confidence interval [CI]: 61.5-66.4) in the exposed group and 60.6 months (95% CI: 56.9-64.2) in the non-exposed, with no significant difference (log-rank [Mantel-Cox] test). Overall survival rates were comparable; 2/148 (1.4%) and 4/111 (3.6%) patients died, in exposed and non-exposed groups, respectively, during the period analysed. Mean overall survival times were 67.2 months (95% CI: 66.2-68.2) in the exposed group and 65.9 months (95% CI: 64.0-67.9) in the unexposed, with no significant difference (log-rank [Mantel-Cox] test)., Conclusions: This study suggests that ovarian stimulation in patients with early-stage breast cancer is safe in the long term., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Endometrial receptivity is a limiting step in human reproduction. A disruption in the development of endometrial receptivity is responsible for recurrent implantation failures (RIF) of endometrial origin. To understand the molecular mechanisms behind the endometrial receptivity process, we used the isobaric tag for relative and absolute quantitation (iTRAQ) method to compare three different endometrial statuses: fertile women, intrauterine device (IUD) carriers, and RIF patients. Overall, iTRAQ allowed identified 1889 non-redundant proteins. Of these, 188 were differentially expressed proteins (DEP) (p-value < .05). Pairwise comparisons revealed 133 significant DEP in fertile vs. IUD carriers and 158 DEP in RIF vs. IUD carriers. However, no DEP were identified between fertile and RIF patients. Western blot validation of three DEP involved in endometrial receptivity (plastin 2, lactotransferrin, and lysozyme) confirmed our iTRAQ results. Moreover, functional KEGG enrichment revealed that complement and coagulation cascades and peroxisome were the two most significant pathways for the RIF vs. IUD comparison and ribosome and spliceosome for the fertile vs. IUD comparison, as possible important pathways involved in the endometrial receptivity acquisition. The lack of DEP between fertile and RIF patient endometria suggest that idiopathic RIF may not have an endometrial origin, with other as-yet-unknown factors involved. SIGNIFICANCE: A pilot study where a comparison of the endometrial protein profile from women with different endometrial receptive grade (fertile women, IUD carriers and RIF patients) during the same period of time (overlapping with the window of implantation) of a hormone replacement therapy was performed using a high-throughput proteomic technique. This approach lead us to better understand the molecular mechanisms undergoing endometrial receptivity, a time-limiting step to achieve pregnancy in humans. Moreover, the number of samples per group (10 Fertile women, 10 IUD carriers and 8 RIF patients) according to the methodology here employed (8plex iTRAQ), give more robustness to our results. Our findings confirm that an IUD introduces numerous changes in the endometrial protein profile when compared to fertile and RIF endometria, revealing some key proteins involved in endometrial receptivity. Finding no significant differences between Fertile and RIF patient endometria could suggest that other as-yet-unknown factors could be involved in the etiology of idiopathic RIF., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This issue's of Views and Reviews considers the origins of lifetime health established around the time of conception in some prevalent conditions related to infertility. Reviews will look at the effects of advanced paternal and maternal age, the influence of the severe sperm factor, and the impact of some endocrinopathies commonly seen in infertile couples, especially women, like polycystic ovary syndrome, under- and overweight, diabetes, and thyroid disorders. The aim of this Views and Reviews section is to summarize current evidence on the consequences of these conditions on postnatal health to encourage research in this field and the need to develop strategies and preventative measures to reduce or prevent unfavorable outcomes in future generations., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Parental excess weight and especially pregestational maternal obesity and excessive weight gain during pregnancy have been related to an increased risk of metabolic (obesity, type 2 diabetes, cardiovascular disease, metabolic syndrome) and nonmetabolic (cancer, osteoporosis, asthma, neurologic alterations) diseases in the offspring, probably mediated by epigenetic mechanisms of fetal programming. Maternal underweight is less common in developed societies, but the discrepancy between a poor nutritional environment in utero and a normal or excessive postnatal food supply with rapid growth catch-up appears to be the main candidate mechanism of the development of chronic diseases during the offspring's adulthood. The role of the postnatal environment in both scenarios (parental overweight or underweight) also seems to influence the offspring's health. Lifestyle interventions before and during pregnancy in both parents, but especially in the mother, as well as in children after birth, are advisable to counteract the many undesirable chronic conditions described., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Hysteroscopic septum resection in women with unfavourable reproductive and clinical outcomes has become common practice worldwide to improve reproductive results. No clear evidence on the possible advantages and drawbacks of this procedure has been published. In this opinion paper, based on a SWOT (strengths, weaknesses, opportunities, threats) analysis, the different aspects of this strategy are evaluated. Currently, no level 1 published evidence supports uterine resection in women with septate uterus. Clinical evidence from the studies analysed matches the more recent guidelines and suggests an improvement in reproductive outcomes after hysteroscopic resection of the septum, particularly in infertile women and women who have experienced recurrent miscarriages. In a patient with no history of infertility or prior pregnancy loss, it may be reasonable to consider septum incision after counselling about the potential risks and benefits of the procedure. Published clinical data in favour of the intervention, however, are based on studies with important methodological limitations. In this situation, the clinician and patient should reach an agreement together, based on the pros and cons of this intervention. Well-designed randomized controlled trials are required to confirm the clinical benefits and cost-effectiveness of this procedure., (Copyright © 2018. Published by Elsevier Ltd.)

Innovations in assisted reproductive technologies (ART) have driven progress in the donor egg field since the birth of the first baby derived from a donor egg in 1983. Over time, donor oocytes have become an increasingly used option for patients unable to conceive with autologous oocytes. In donor egg, the unique separation of the oocyte source and recipient uterus has created a model that has propelled advances in ART. Progressive ART innovations that have optimized the oocyte donor and resulting embryo include the following: evaluation of ovarian reserve, controlled ovarian hyperstimulation regimens that reduce the risk of ovarian hyperstimulation syndrome, blastocyst culture, oocyte cryopreservation, and preimplantation genetic testing. For donor egg recipients, methods to optimize the endometrium to maximize implantation include endometrial receptivity testing, immunologic donor-recipient matching, and increased understanding of the uterine microbiome., (Copyright © 2018. Published by Elsevier Inc.)

Research Question: Can gonadotrophin releasing hormone (GnRH) antagonist be used in egg donation recipients with ovulatory cycles for the purpose of achieving synchronization between the donor´s and recipient´s cycle?, Design: Prospective randomized controlled trial to compare 7-day dosage of GnRH antagonist for endometrial priming in an oocyte donation programme with a single dose of long-acting GnRH agonist. A total of 563 women were randomized in a private single centre, and 473 women underwent embryo transfer. Ongoing pregnancy rate was the primary end point. Analysis was adjusted for embryonic stage at the time of embryo transfer; data collected included days on the waiting list; number of fresh-vitrified oocytes collected; and oocyte donor´s age at the time of retrieval., Results: No statistically significant differences were found between groups in per intention-to-treat analysis: adjusted OR 1.42 (CI 0.97 to 2.09); per treatment received: adjusted OR 1.43 (CI 0.97 to 2.09); per embryo transfer: adjusted OR for ongoing pregnancy rate 1.47 (CI 1.01 to 2.13), P = 0.047., Conclusions: For women with ovulatory cycles undergoing oocyte donation, the outcomes are similar between GnRH antagonist and down-regulated hormone replacement protocols., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose of Review: To review recent findings related to possible causes of recurrent implantation failure of endometrial origin in normal uterus., Recent Findings: Recent evidences suggest that in apparently normal endometria, RIF may associate with molecular and functional changes in the uterus such as abnormal endometrial microbiota, including the presence of chronic endometritis, poor synchronization between the blastocyst and endometrium, and/or excessive uterine peristalsis. An altered endometrial microbiota detected by molecular techniques has been recently related to poorer embryo implantation, even in apparently normal endometria. The use of the endometrial receptivity analysis test to obtain an objective signature of endometrial receptivity has shown to improve the reproductive performance in RIF patients. The diagnosis of uterine peristalsis, however, remains challenging since the usual evaluation by transvaginal ultrasound is not accurate, and drugs tested to reduce uterine peristalsis and enhance embryo implantation have not been clearly beneficial. Finally, endometrial injury to improve implantation rates remains controversial being definitive well-designed trials needed to assess its benefit, if any., Summary: In recurrent implantation failure of endometrial origin an altered pattern of the microbial endometrial ecosystem, a displaced window of implantation leading to desynchronization between the blastocyst and the endometrium, or an altered pattern of uterine contractions during embryo transfer may be factors to consider in our attempt to solve this clinical issue. New diagnostics for assessing these conditions and new therapies to improve these dysfunctional situations are currently under investigation to be presumably included in the near future in the work-up of affected patients.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women and the main cause of infertility due to anovulation. However, this syndrome spans the lives of women affecting them from in-utero life until death, leading to several health risks that can impair quality of life and increase morbidity and mortality rates. Fetal programming may represent the beginning of the condition characterized by hyperandrogenism and insulin resistance which leads to a series of medical consequences in adolescence, adulthood, and old age. Menstrual and fertility problems evolve into metabolic complications as age advances. An early and precise diagnosis is important for an adequate management of PCOS, especially at the extreme ends of the reproductive lifespan. However, many different phenotypes are included under the same condition, being important to look at these different phenotypes separately, as they may require different treatments and have different consequences. In this way, PCOS exhibits a great metabolic complexity and its diagnosis needs to be revised once again and adapted to recent data obtained by new technologies. According to the current medical literature, lifestyle therapy constitutes the first step in the management, especially when excess body weight is associated. Pharmacotherapy is frequently used to treat the most predominant manifestations in each age group, such as irregular menses and hirsutism in adolescence, fertility problems in adulthood, and metabolic problems and risk of cancer in old age. Close surveillance is mandatory in each stage of life to avoid health risks which may also affect the offspring, since fetal and post-natal complications seem to be increased in PCOS women.

Objective: To determine the clinical value of preimplantation genetic diagnosis for aneuploidy screening (PGD-A) in women of advanced maternal age (AMA; between 38 and 41 years)., Design: This was a multicenter, randomized trial with two arms: a PGD-A group with blastocyst transfer, and a control group with blastocyst transfer without PGD-A., Setting: Private reproductive centers., Patient(s): A total of 326 recruited patients fit the inclusion criteria, and 205 completed the study (100 in the PGD-A group and 105 in the control group)., Intervention(s): Day-3 embryo biopsy, array comparative genomic hybridization, blastocyst transfer, and vitrification., Main Outcome Measure(s): Primary outcomes were delivery and live birth rates in the first transfer and cumulative outcome rates., Result(s): The PGD-A group exhibited significantly fewer ETs (68.0% vs. 90.5% for control) and lower miscarriage rates (2.7% vs. 39.0% for control). Delivery rate after the first transfer attempt was significantly higher in the PGD-A group per transfer (52.9% vs 24.2%) and per patient (36.0% vs. 21.9%). No significant differences were observed in the cumulative delivery rates per patient 6 months after closing the study. However, the mean number of ETs needed per live birth was lower in the PGD-A group compared with the control group (1.8 vs. 3.7), as was the time to pregnancy (7.7 vs. 14.9 weeks)., Conclusion(s): Preimplantation genetic diagnosis for aneuploidy screening is superior compared with controls not only in clinical outcome at the first ET but also in dramatically decreasing miscarriage rates and shortening the time to pregnancy., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the transcriptomic profile of endometrial gene alterations during the window of implantation in infertile obese patients., Design: Multicenter, prospective, case-control study., Setting: Three academic medical centers for reproductive medicine., Patient(s): Infertile patients, stratified into body mass index (BMI) categories according to the World Health Organization guidelines, were included in the study., Intervention(s): Endometrial samples were obtained from women undergoing standardized estrogen and P replacement cycles after 5 days of vaginal P supplementation., Main Outcome Measure(s): To identify endometrial gene expression alterations that occur during the window of implantation in infertile obese patients as compared with infertile normal-weight controls using a microarray analysis., Result(s): XCL1, XCL2, HMHA1, S100A1, KLRC1, COTL1, COL16A1, KRT7, and MFAP5 are significantly dysregulated during the window of implantation in the receptive endometrium of obese patients. COL16A1, COTL1, HMHA1, KRCL1, XCL1, and XCL2 were down-regulated and KRT7, MFAP5, and S100A1 were up-regulated in the endometrium of obese patients. These genes are mainly involved in chemokine, cytokine, and immune system activity and in the structural extracellular matrix and protein-binding molecular functions., Conclusion(s): Obesity is associated with significant endometrial transcriptomic differences as compared with non-obese subjects. Altered endometrial gene expression in obese patients may contribute to the lower implantation rates and increased miscarriage rates seen in obese infertile patients., Clinical Trial Registration Number: NCT02205866., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The endometrium is one of a number of factors involved in achieving optimal outcomes after assisted reproductive treatment. Owing to its "passive" growth following adequate ovarian stimulation, it has received virtually no attention. Only when either endometrial thickness or ultrasonographic pattern seem inadequate have different strategies been assessed to try to improve it, especially in those cases where it seems difficult or impossible to make it grow. The objective of this review is to summarize the different strategies that have been investigated in patients with inadequate endometrium, to attempt to provide solid evidence of therapies that may be beneficial and to move away from empirism. A review of the existing literature was performed by searching MEDLINE, EMBASE, Cochrane library and Web of Science for publications in English related to refractory endometrium. Most current treatments are based on anecdotal cases and not on solid data, although worldwide many doctors and patients use them. In conclusion, this review found that it is not easy to provide a pragmatic, evidence-based approach to help physicians and patients confused by the available data on how to improve a poor endometrium. Honest balanced information provided to our patients is the best that we can do., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine whether the global metabolomic profile of the spent culture media (SCM) of day-3 embryos is different in obese and normoweight women undergoing in vitro fertilization (IVF)., Design: Prospective cohort analysis., Setting: IVF clinic., Patient(s): Twenty-eight young, nonsmoking women with normoweight, nonsmoking male partners with mild/normal sperm factors undergoing a first IVF attempt for idiopathic infertility, tubal factor infertility, or failed ovulation induction: obese ovulatory women (n = 12); obese women with polycystic ovary syndrome (PCOS; n = 4); normoweight ovulatory women (n = 12)., Intervention(s): Fifty μl of SCM collected from two day-3 embryos of each cohort., Main Outcome Measure(s): Metabolomic profiling via ultrahigh performance liquid chromatography coupled to mass spectrometry of SCM from a total of 56 embryos., Result(s): The untargeted metabolomic profile was different in obese and normoweight women. Partial least squares discriminant analysis resulted in a clear separation of samples when a total of 551 differential metabolites were considered. A prediction model was generated using the most consistent metabolites. Most of the metabolites identified were saturated fatty acids, which were detected in lower concentrations in the SCM of embryos from obese women. The metabolomic profile was similar in obese women with or without PCOS., Conclusion(s): The metabolomic profile in the SCM of day-3 embryos is different in normoweight and obese women. Saturated fatty acids seem to be reduced when embryos from obese patients are present., Clinical Trial Registration Number: NCT01448863., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Assisted reproduction technology (ART) has become a standard treatment for infertile couples. Increased success rates obtained over the years have resulted primarily from improved embryo quality, but implantation rates still remain lower than expected. The uterus, an important player in implantation, has been frequently neglected. While a number of uterine pathologies have been associated with decreased natural fertility, less information exists regarding the impact of these pathologies in ART. This report reviews the evidence to help clinicians advise ART patients., Methods: An electronic search of PubMed and EMBASE was performed to identify articles in the English, French or Spanish language published until May 2014 which addressed uterine pathology and ART. Data from natural conception were used only in the absence of data from ART. Studies were classified in decreasing categories: RCTs, prospective controlled trials, prospective non-controlled trials, retrospective studies and experimental studies. Studies included in lower categories were only used if insufficient evidence was available. Pooled data were obtained from systematic reviews with meta-analyses when available. The summary of the evidence for the different outcomes and the degree of the recommendation for interventions were based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) statement recommendations., Results: There is strong evidence that surrogacy is effective for uterine agenesia. For the remaining pathologies, however, there is very little evidence that the established treatments improve outcomes, or that these pathologies have a negative effect on ART. In the presence of an apparently normal uterus, assessing endometrial receptivity (ER) is the goal; however diagnostic tests are still under development., Conclusions: The real effect of different uterine/endometrial integrity pathologies on ART is not known. Moreover, currently proposed treatments are not based on solid evidence, and little can be done to assess ER in normal or abnormal conditions. No strong recommendations can be given based on the published experience, bringing an urgent need for well-designed studies. In this context, we propose algorithms to study the uterus in ART., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This prospective longitudinal study aimed at comparing maternal immune response among naturally conceived (NC; n = 25), in vitro fertilization (IVF; n = 25), and egg donation (ED; n = 25) pregnancies. The main outcome measures were, firstly, to follow up plasma levels of interleukin (IL) 1 beta, IL2, IL4, IL5, IL6, IL8, IL10, IL17, interferon gamma, tumor necrosis factor-alpha (TNFα), transforming growth factor-beta (TGFβ), regulated upon activation normal T-cell expressed and secreted (RANTES), stromal cell-derived factor 1 alpha (SDF1α), and decidual granulocyte-macrophage colony-stimulating factor (GM-CSF) during the three trimesters of pregnancy during the three trimesters of pregnancy; secondly, to evaluate if the cytokine and chemokine pattern of ED pregnant women differs from that of those with autologous oocytes and, thirdly, to assess if women with preeclampsia show different cytokine and chemokine profile throughout pregnancy versus women with uneventful pregnancies. Pregnant women in the three study groups displayed similar cytokine and chemokine pattern throughout pregnancy. The levels of all quantified cytokines and chemokines, except RANTES, TNFα, IL8, TGFβ, and SDF1α, rose in the second trimester compared with the first, and these higher values remained in the third trimester. ED pregnancies showed lower SDF1α levels in the third trimester compared with NC and IVF pregnancies. Patients who developed preeclampsia displayed higher SDF1α plasma levels in the third trimester.