Do clinical outcomes differ for day-5 versus day-6 single embryo transfers controlled for endometrial factor?

RESEARCH QUESTION: Is there is a difference in clinical outcomes between day-5 versus day-6 blastocysts when transferred in a personalized embryo transfer (PET) cycle guided by Endometrial Receptivity Analysis (ERA)? DESIGN: Multicentre, retrospective study; 260 patients who underwent a single embryo transfer with either a day-5 or day-6 blastocyst in a PET cycle guided by ERA between January 2017 and December 2019. RESULTS: A total of 260 blastocysts were transferred in a single embryo PET cycle guided by ERA. Of those, 183 (70.4%) were day-5 blastocysts and 77 (29.6%) were day-6 blastocysts. Clinical outcomes were similar when transferring day-5 blastocysts versus day-6 blastocysts: pregnancy rate was 75.4% (138/183) and 70.1% (54/77) (P = 0.465); implantation rate was 67.8% (124/183) and 63.6% (49/77) (P = 0.476); and ongoing pregnancy rate was 57.9% (106/183) and 58.4% (45/77) (P = 0.728), respectively. CONCLUSIONS: The data suggest that the clinical potential of day-5 and day-6 blastocysts are similar, as no difference in clinical outcomes are observed when transferring at the time of optimal endometrial receptivity as determined by ERA.

Bases anatómicas del colgajo anterolateral de muslo de flujo inverso / Anatomical basis of distally based anterolateral thigh flap

Introducción y objetivo: El colgajo anterolateral de muslo de base distal presenta una alternativa interesante para la reconstrucción de los defectos cutáneos de la rodilla.El motivo de este trabajo es el estudio anatómico de la arteria descendente de la circunfleja femoral lateral y su existencia o no de anastomosis distal, que nos permitirá la realización del colgajo basado distalmente.Material y método.Estudiamos diferentes ítems en 22 miembros inferiores formolizados: origen de la arteria, distancia desde la salida de la perforante de la arteria descendente hasta la piel, longitud y localización de la arteria descendente, anastomosis distal en el caso de que la hubiera, localización del punto pivote tomando como punto de referencia la esquina súpero-lateral de la patela y la suma de la longitud de la perforante, y la longitud de la arteria de la descendente que nos da la longitud del pedículo que podemos obtener al disecar el colgajo.Resultados.En relación con la anastomosis distal describimos 2 modelos. Modelo 1: no anastomosis, con una proporción del 45%; y modelo 2: anastomosis distal existente, con un 55%. En el modelo 2 establecemos a su vez 3 tipos de anastomosis: tipo 1, cuando la anastomosis se realiza con la arteria geniculada lateral superior, en un 42%; tipo 2, anastomosis con la arteria femoral profunda, en un 25%; y tipo 3, anastomosis con ambas, en un 33%.El punto pivote lo encontramos como media a 11 cm del borde superior de la patela. La longitud del pedículo presentó una media de 15 cm.Conclusiones.Nuestros resultados demuestran que el colgajo anterolateral de base distal es una adecuada alternativa para la cobertura de pérdidas de sustancia en la rodilla. Para emplearlo, debido a la diversidad anatómica, sería adecuado realizar una angiografía previa o una revisión intraoperatoria de la anastomosis distal. (AU)

Background and objective: The distally based anterolateral thigh flap is an interesting alternative for the reconstruction of skin defects of the knee.The reason for this paper is the anatomical study of the descending artery of the lateral circumflex femoral and the existence or not of a distal anastomosis that allows us to perform the distally based flap.Methods.Different items were studied in 22 embalmed lower limbs: origin of the artery, distance from the outlet of the perforator of the descending artery to the skin, length and location of the descending artery, distal anastomosis if any, location of the pivot point taking as a reference point the supero-lateral corner of the patella, and the sum of the length of the perforator and the length of the descending artery, which gives us the length of the pedicle that we can obtain by dissecting the flap.Results.Related to the distal anastomosis, we described 2 models. Model 1: no anastomosis, with a ratio of 45%, and model 2: there is an anastomosis in 55%. In model 2 we have established 3 types of anastomosis: type 1, when the anastomosis is performed with the superior lateral geniculate artery, in 42%; type 2, anastomosis with the deep femoral artery, in 25%; and type 3, anastomosis with both, in 33%. The pivot point was found an average of 11 cm from the upper edge of the patella.The length of the pedicle had an average of 15 cm.Conclusions.Our results demonstrate that the distally based anterolateral flap is an adequate alternative for knee soft-tissue reconstruction. Due to the anatomical diversity, angiography or intraoperative revision of the distal anastomosis would be appropriate to perform this flap. (AU)

Obesity Affects Endometrial Receptivity by Displacing the Window of Implantation.

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/m2; n = 44), overweight (25-29.9 kg/m2; n = 29), class I obese (30.0-34.9 kg/m2; n = 54), and class II and III obese (> 35 kg/m2; 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.

Endometrial Receptivity Analysis (ERA): data versus opinions.

This article summarises and contextualises the accumulated basic and clinical data on the ERA test and addresses specific comments and opinions presented by the opponent as part of an invited debate. Progress in medicine depends on new technologies and concepts that translate to practice to solve long-standing problems. In a key example, combining RNA sequencing data (transcriptomics) with artificial intelligence (AI) led to a clinical revolution in personalising disease diagnosis and fostered the concept of precision medicine. The reproductive field is no exception. Translation of endometrial transcriptomics to the clinic yielded an objective definition of the limited time period during which the maternal endometrium is receptive to an embryo, known as the window of implantation (WOI). The WOI is induced by the presence of exogenous and/or endogenous progesterone (P) after proper oestradiol (E2) priming. The window lasts 30-36 hours and, depending on the patient, occurs between LH + 6 and LH + 9 in natural cycles or between P + 4 and P + 7 in hormonal replacement therapy (HRT) cycles. In approximately 30% of IVF cycles in which embryo transfer is performed blindly, the WOI is displaced and embryo-endometrial synchrony is not achieved. Extending this application of endometrial transcriptomics, the endometrial receptivity analysis (ERA) test couples next-generation sequencing (NGS) to a computational predictor to identify transcriptomic signatures for each endometrial stage: proliferative (PRO), pre-receptive (PRE), receptive (R) and post-receptive (POST). In this way, personalised embryo transfer (pET) may be possible by synchronising embryo transfer with each patient's WOI. Data are the only way to confront arguments sustained in opinions and/or misleading concepts; it is up to the reader to make their own conclusions regarding its clinical utility.

Arteria mediana persistente: una variación anatómica vascular en el miembro superior. Estudio anatómico, revisión bibliográfica y estudio clínico en 128 pacientes / Persistent median artery: a vascular anatomical variation in the upper limb. Anatomical study, bibliographic review and clinical study in 128 patients

Introducción y objetivo: En nuestra práctica diaria encontramos variaciones anatómicas que tienen repercusión tanto diagnóstica como terapéutica. Con este artículo ponemos el acento en la importancia de las variaciones anatómicas vasculares, presentando un caso anatómico de arteria mediana persistente que altera la vascularización de los dedos de la mano y que frecuentemente se asocia a la presencia de un nervio mediano bífido. Tras este hallazgo, realizamos una revisión bibliográfica y un estudio clínico para poner en relieve la asociación de esta malformación con el síndrome del túnel carpiano (STC). Material y método: Dividimos nuestro estudio en 2 partes: una anatómica y otra clínica. El estudio anatómico de un antebrazo presentó como hallazgo una arteria mediana palmar persistente responsable de la vascularización del 1er y 2º dedos de la mano, asociada a un nervio mediano bífido. Continuamos con una revisión bibliográfica y un estudio prospectivo para conocer el porcentaje de arterias medianas encontradas en la cirugía del STC en pacientes escogidos de manera aleatoria en función de su incorporación a la lista de espera de nuestro hospital durante un periodo de 4 meses. Resultados: Fueron intervenidos 128 pacientes de STC encontrando arteria mediana persistente en 3 casos, lo que corresponde a un 2.34% del total valorado. Discusión: El porcentaje de presentación de arteria mediana persistente en nuestro estudio coincide con los diversos estudios revisados en adultos. Coincidimos con ellos en la importancia del conocimiento de las variaciones anatómicas por si mismas y de su implicación en la sintomatología del STC. También es importante tenerlas en cuenta cuando nos enfrentamos a una lesión traumática o cuando disecamos un colgajo

Background and objective: In our daily practice we find anatomical variations that will have a diagnostic and therapeutic repercussion. With this article we emphasize the importance of vascular anatomical variations presenting an anatomical case of a persistent median artery which alters the vascularization of the fingers, and that is frequently associated with the presence of a bifid median nerve. Following this finding, a literature review and a clinical study were conducted to highlight the association of this malformation with carpal tunnel syndrome (STC) Methods: Our study is divided into two parts: anatomical and clinical. The anatomical study of a forearm showed us as a persistent median palmar artery which is responsible for vascularization of the 1st and 2nd fingers, associated with a bifid median nerve. Then, we conducted a literature review and a prospective study in order to know the percentage of medium arteries found in the STC surgery, chosen in a random way based on their incorporation to the waiting list of our hospital for a 4 months period. Results: A total of 128 STC patients were operated, finding a persistent median artery in 3 patients, which corresponds to 2.34% of the total valued. Discussion: The percentage of presentation of persistent medium artery in our study is coincident with the various studies reviewed in adult patients. We agree on the importance of the knowledge of anatomical variations by themselves and their implication in the symptomatology of STC. It is also important to keep in mind the existence of these anatomical variations when faced with a traumatic injury or when we dissect a flap

Window of implantation transcriptomic stratification reveals different endometrial subsignatures associated with live birth and biochemical pregnancy.

OBJECTIVE: To refine the endometrial window of implantation (WOI) transcriptomic signature by defining new subsignatures associated to live birth and biochemical pregnancy. DESIGN: Retrospective cohort study. SETTING: University-affiliated in vitro fertilization clinic and reproductive genetics laboratory. PATIENT(S): Healthy fertile oocyte donors (n = 79) and patients with infertility diagnosed by Endometrial Receptivity Analysis (n = 771). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): WOI transcriptomic signatures associated with specific reproductive outcomes. RESULT(S): The retrospective cohort study was designed to perform a prediction model based on transcriptomic clusters for endometrial classification (training set, n = 529). The clinical follow-up set in the expected WOI (n = 321) was tested with the transcriptomic predictor to detect WOI variability and the pregnancy outcomes associated with these subsignatures (n = 228). The endometrial receptivity signature was redefined into four WOI transcriptomic profiles. This stratification identified an optimal endometrial receptivity (RR) signature resulting in an ongoing pregnancy rate (OPR) of 80% in terms of live birth, as well as a late receptive-stage (LR) signature with a potential high risk of 50% biochemical pregnancy. Abnormal down-regulation of the cell cycle was the main dysregulated function among the 22 genes associated with biochemical pregnancy. CONCLUSION(S): The major differences between the WOI transcriptomic stratification were in the OPR and biochemical pregnancy rate. The OPR ranged from 76.9% and 80% in the late prereceptive (LPR) and RR signatures, respectively, versus 33.3% in the LR. The biochemical pregnancy rate was 7.7% and 6.6% in LPR and RR, respectively, but 50% in LR, which highlights the relevance of endometrial status in the progression of embryonic implantation.

Endometrial receptivity in eutopic endometrium in patients with endometriosis: it is not affected, and let me show you why.

Many women with endometriosis experience compromised fertility. This disease clearly exerts quantitative damage on the ovaries, and perhaps, also qualitative damage. However, it remains controversial whether endometrial receptivity is compromised. Here we review the evidence from basic transcriptomic signature data to clinical data from an oocyte donation model and find support for the concept that endometrial receptivity is not impaired in women with endometriosis when healthy embryos reach the endometrial cavity.

Does an increased body mass index affect endometrial gene expression patterns in infertile patients? A functional genomics analysis.

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.

Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial.

STUDY QUESTION: Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? SUMMARY ANSWER: Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. WHAT IS KNOWN ALREADY: The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. STUDY DESIGN, SIZE, DURATION: Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. PARTICIPANTS/MATERIALS, SETTING, METHODS: Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT-PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. MAIN RESULTS AND THE ROLE OF CHANCE: Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were significantly elevated in the endometrium of hCG-treated patients, consistent with earlier staging. The ERA did not predict an overall positive impact of intrauterine hCG on endometrial receptivity. However, ACTA2, encoding α-SMA was significantly increased in response to intrauterine hCG. Similar to the hCG-treated non-human primate, sub-epithelial and peri-vascular α-SMA expression was induced in women following hCG infusion. Other known targets of hCG in the baboon were also found to be increased, including C3 and NOTCH1, which have known roles in endometrial receptivity. LIMITATIONS, REASONS FOR CAUTION: This study differs from our previous work in the hCG-treated non-human primate along with clinical studies in infertile patients. Specifically, we performed a single intrauterine infusion in oocyte donors instead of either continuous hCG via an osmotic mini-pump in the baboon or infusion followed by blastocyst-derived hCG in infertile women undergoing embryo transfer. Therefore, the full impact of intrauterine hCG in promoting endometrial receptivity may not have been evident. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest a potential clinical benefit for intrauterine hCG prior to embryo transfer on Day 3 in counteracting endometrial dyssynchrony from ovarian stimulation and promoting expression of markers important for stromal survival. Finally, there were no obvious negative effects of intrauterine hCG treatment. STUDY FUNDING/COMPETING INTERESTS: Funding for this work was provided by NICHD R01 HD042280 (A.T.F.) and NICHD F30 HD082951 (M.R.S.). C.S. and P.D.-G are co-inventors of the patented ERA, which is owned by IGENOMIX SL and was used in this study, and C.S. is a shareholder in IGENOMIX SL. M.R.-A. is employed by IGENOMIX SL. No other authors have any conflicts of interest to report. TRIAL REGISTRATION NUMBER: This study was registered with ClinicalTrials.gov (NCT01786252). TRIAL REGISTRATION DATE: 5 February 2013. DATE OF FIRST PATIENT'S ENROLLMENT: 10 May 2013.

Both slowly developing embryos and a variable pace of luteal endometrial progression may conspire to prevent normal birth in spite of a capable embryo.

Embryonic implantation requires synchrony between the endometrium and the embryo. When analyzed in isolation, competent embryos may be unsuccessful when placed on a nonreceptive endometrium or vice versa, contributing to the "black box" of implantation failure. It is when the two are assessed together that dyssynchrony becomes evident, due to premature progesterone stimulus on the endometrium, physiologic displacement of the window of implantation or late blastulation of the embryo, or all combined. From the embryonic component, detailed assessment of the timing of blastulation is essential. The molecular diagnosis of endometrial receptivity based on its transcriptomic signature could be superior to other techniques used in the past for defining the endometrial window of implantation.

Is endometrial receptivity transcriptomics affected in women with endometriosis? A pilot study.

Endometrial receptivity is still questioned today in women with endometriosis. The aim of this study was to assess the endometrial receptivity gene signature in patients with different stages of endometriosis by investigating transcriptomic modifications of their endometrium using the endometrial receptivity array (ERA) test. A prospective, interventional multicentre pilot trial was designed and implemented in two university-affiliated infertility units from Belgium and Spain. Gene expression microarray was used to diagnose the receptivity status by quantifying the expression of 238 specific genes directly related to human endometrial receptivity. Unsupervised hierarchical clustering showed no clustering of samples based on endometriosis stages. Two subgroups of samples clustered together corresponding on the day of the cycle in which the biopsy was taken (day 18 versus days 19-20). None of the 238 genes present in the ERA array were significantly over- or under- expressed in any of different stages of the disease compared with controls. Minimal differences were found when looking at the functional profile, suggesting that the possible effect from a clinical point of view may be meaningless. Endometrial receptivity gene signature during the implantation window does not vary significantly among patients with endometriosis even considering different stages compared with healthy women.

Human Endometrial Transcriptomics: Implications for Embryonic Implantation.

Human endometrium has been extensively investigated in the search for markers capable of predicting its receptive status. The completion of the Human Genome Project has triggered a rapid development of new fields in molecular biology, the "transcriptomics" being a major turning point in the knowledge acquisition of endometrial receptivity. Based on this, a customized Endometrial Receptivity Array (ERA) has been developed, which is capable of identifying the genomic signature of receptivity. This diagnostic tool showed that the window of implantation (WOI) is displaced in one out of four patients with implantation failure, allowing the identification of their personalized WOI. This strategy allows performing a personalized embryo transfer (pET) on the day in which the endometrium is receptive. The combination of a systems biology approach and next-generation sequencing will overcome the limitations of microarrays, and will, in the future, allow elucidation of the mechanisms involved in embryo implantation.

Timing the window of implantation by nucleolar channel system prevalence matches the accuracy of the endometrial receptivity array.

OBJECTIVE: To test if nucleolar channel system (NCS) prevalence matches the accuracy of the endometrial receptivity array (ERA) for identification of the window of endometrial receptivity. DESIGN: Comparative retrospective study, May 2008-May 2012. SETTING: University-affiliated infertility clinic. PATIENT(S): Forty-nine healthy oocyte donors, regularly cycling, aged 20-34 years with a body mass index of 19-25 kg/m2. INTERVENTION(S): Endometrial biopsies were collected throughout the menstrual cycle. All samples underwent transcriptomic signature identification by ERA testing (performed in a prior study) and quantification of NCS prevalence by using indirect immunofluorescence (performed in the present study). MAIN OUTCOME MEASURE(S): Concordance of ERA results determining the window of implantation with NCS prevalence was statistically analyzed using the kappa index. Based on dating according to the luteinizing hormone surge, specimens were dichotomized into receptive (n=24) and nonreceptive (n=25). The NCS prevalence was expressed as percentage of NCSs per endometrial epithelial cells in each endometrial biopsy. RESULT(S): Concordance of ERA and NCS dating vs. luteinizing hormone yielded comparable kappa indices of 0.878 and 0.836, respectively. Direct comparison of ERA and NCS dating resulted in a kappa index of 0.796. CONCLUSION(S): Prevalence of NCS identifies the window of endometrial receptivity previously identified by their transcriptomic signature using the ERA.

Transcriptomics of the human endometrium.

During the mid-secretory phase, the endometrium acquires the receptive phenotype, which corresponds to the only period throughout the endometrial cycle in which embryo implantation is viable. Endometrial receptivity is a crucial process and even more important in Assisted Reproductive Technologies (ART) where embryo-endometrial synchronization is coordinated through embryo transfer timing. Over the last decade, transcriptomic analyses performed on the human endometrium have shown that specific genomic signatures can be used to successfully phenotype different phases of the menstrual cycle including the receptive stage, independently of the histological appereance of the endometrial tissue. In this paper, we review current evidence demonstrating that endometrial transcriptomics objectively identifies the implantation window in a personalized manner, opening the field for the diagnosis of the endometrial factor in ART and moving to stratified medicine at this level, using microarray technology and soon high-throughput next generation sequencing coupled with functional and systems genomics approach.

Clinical management of endometrial receptivity.

The endometrial window of implantation (WOI), the cycle days during which normal embryo implantation can occur, has generally been assumed to begin on cycle day 19 or 20 of an idealized 28 days cycle and last for 4 to 5 days. Noyes et al took the first steps in defining the WOI by establishing a set of morphological criteria to evaluate endometrial development and receptivity, but recent studies have invalidated their use in the routine evaluation of infertility. Based on greater than 10 years of extensive research, our group has developed a molecular diagnostic tool (the endometrial receptivity array [ERA] test) based on the specific transcriptomic signature that identifies the receptive endometrium in natural and artificial (hormonal replacement therapy) cycles. The ERA test has shown that some patients have a delayed WOI, others have an advanced WOI, and others can have unusually short windows of receptivity. This identification and characterization of the WOI allows the personalization of the embryo transfer. In this review, we describe the ERA and our experience with its use in assessment of the endometrial receptivity in patients undergoing assisted reproduction.

The impact of using the combined oral contraceptive pill for cycle scheduling on gene expression related to endometrial receptivity.

STUDY QUESTION: Does the combined oral contraceptive pill (COCP) change endometrial gene expression when used for cycle programming? SUMMARY ANSWER: COCP used for scheduling purposes does not have a significant impact on endometrial gene expression related to endometrial receptivity. WHAT IS KNOWN ALREADY: Controversy exists around COCP pretreatment for IVF cycle programming, as some authors claim that it might be detrimental to the live birth rate. Microarray technology applied to the study of tissue gene expression has previously revealed the behavior of genes related to endometrial receptivity under different conditions. STUDY DESIGN, SIZE, AND DURATION: Proof-of-concept study of 10 young healthy oocyte donors undergoing controlled ovarian stimulation (COS) recruited between June 2012 and February 2013. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: Microarray data were obtained from endometrial biopsies from 10 young healthy oocyte donors undergoing COS with GnRH antagonists and recombinant FSH. In group A (n = 5), COCP pretreatment was used for 12-16 days, and stimulation began after a 5-day pill-free interval. Stimulation in group B (n = 5) was initiated on cycle day 3 after a spontaneous menses. Endometrial biopsies were collected 7 days after triggering with hCG. MAIN RESULTS AND THE ROLE OF CHANCE: No individual genes exhibited increased or decreased expression (fold change (FC) >2) in patients with prior COCP treatment (group A) compared with controls (group B). However, the results of the functional analysis showed a total of 11 biological processes that were significantly enriched in group A compared with group B (non-COCP). LIMITATIONS, REASONS FOR CAUTION: The Endometrial Receptivity Array (ERA) has only been validated on endometrial samples obtained in natural cycles and after hormonal replacement treatment (HRT). Therefore, it was not possible in this study to classify the endometrial samples as receptive or non-receptive. We used the ERA to focus on 238 genes that are intimately related to endometrial receptivity, thus simplifying the analysis and understanding of the data. WIDER IMPLICATIONS OF THE FINDINGS: Cycle scheduling is common in IVF units and is used to avoid weekend retrievals and/or to distribute evenly the workload for better efficiency. Our failure to detect any relevant changes in the genes related to the window of implantation when cycles were programmed with COCP pretreatment suggests that, despite controversial clinical results in previous studies, the use of COCPs in this way does not affect uterine receptivity adversely. STUDY FUNDING/COMPETING INTEREST(S): Funding for this study was provided by an unrestricted grant from Merck Sharp & Dohme. C.S. and A.P. are co-inventors (with Patricia Diaz-Gimeno) of the Endometrial Receptivity Array and hold the patent. The other authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: EudraCT registration number is 2011-003250-34.