LnCRNAs in the Regulation of Endometrial Receptivity for Embryo Implantation.

The development of endometrial receptivity is crucial for successful embryo implantation and the initiation of pregnancy. Understanding the molecular regulatory processes that transform the endometrium into a receptive phase is essential for enhancing implantation rates in fertility treatments, such as in vitro fertilization (IVF). Long non-coding RNAs (lncRNAs) play a pivotal role as gene regulators and have been examined in the endometrium. This review offers current insights into the role of lncRNAs in regulating endometrial receptivity. Considering the significant variation in endometrial remodeling among species, we summarize the key events in the human endometrial cycle and discuss the identified lncRNAs in both humans and other species, which may play a crucial role in establishing receptivity. Notably, there are 742 lncRNAs in humans and 4438 lncRNAs that have the potential to modulate endometrial receptivity. Additionally, lncRNAs regulating matrix metalloproteinases (MMPs) and Let-7 have been observed in both species. Future investigations should explore the potential of lncRNAs as therapeutic targets and/or biomarkers for diagnosing and improving endometrial receptivity in human fertility therapy.

Immune system cells modulation in patients with reproductive issues: A systematic review approach.

The aim of this study was to carry out a systematic literature review to investigate the main immune cells responsible for implantation failures. We selected papers from PubMed, Embase and Virtual Health Library databases. Eligible articles included publications between January 1, 2010 and April 24, 2022. Inclusion criteria were: observational and case-control studies; and the exclusion criteria were: review papers, letters to the editor, abstracts, animal studies and case reports. We extracted the following information: day of collection, number of patients, control group, age of patients, type of sample used, immune cells and cytokines. As main findings in our mapping, we found that in peripheral blood, CD3+, CD4+, CD8+, CD16+, CD56+, CD57+, CD69+, CD154+, CD158a+, NKp46 cells were increased and the CD4+, CD45+, Foxp3 and NKp46 markers were reduced. From the endometrial biopsies, there was an increase in CD3+, CD4+, CD5+, CD8+, CD16+, CD25+, CD45+, CD56+, CD57+, CD68+, CD127+ and a reduction in CD45+, CD56+, NKp46 and FoxP3 cells. Cytokines found increased in peripheral blood included IL-6, IL-10, IL-17, INF-γ, TGF-ß, TNF-α; while IL-4, IL-6, IL-10, IL-35, FoxP3, TGF-ß, SOCS3 were reduced. As for the biopsies, there was an increase in IL-2, IL-6, IL-17, IL-22, IL-23, INF-A1, INF-B1, INF-γ, TNF-R and a reduction in IL-6, IL-10, INF-γ, TGFß, TNF-α. We concluded that immune cells can be modulated during pregnancy failure, but further studies are needed to elucidate the modulating effect of the immune system on the endometrium of these patients.

Lactoferrin affects in vitro and in vivo fertilization and implantation in rats.

Lactoferrin (LF) is present in the oviduct, reduces in vitro gamete interaction, and affects sperm capacitation parameters in humans. Our aim was to investigate LF actions on further stages of the reproductive process in the Wistar rat model. Motile sperm were obtained from cauda epididymis to assess LF binding by direct immunofluorescence and LF effect on acrosome reaction (AR) using a Coomassie blue staining. After ovarian hyperstimulation of female rats, oocytes were surgically recovered and coincubated with motile sperm and different doses of LF to estimate the in vitro fertilization (IVF) rate. To evaluate the LF effect on pregnancy and embryo implantation, female rats (80 days old) were placed with males and received daily intraperitoneal injections of LF during one complete estrous cycle (pregnancy experiments) or during the first 8 gestational days (implantation experiments). The number of pregnant females and live born pups was recorded after labor. Moreover, the number of implantation sites was registered during the implantation period. LF was able to bind to the sperm head, midpiece, and tail. 10 and 100 µg/ml LF stimulated the AR but reduced the IVF rate. The administration of 100 and 200 mg/kg LF significantly decreased the number of implantation sites and the litter size, whereas 100 mg/kg LF declined the pregnancy rate. The results suggest that LF might interfere with the reproductive process, possibly interfering with gamete interaction or inducing a premature AR; nevertheless, the mechanisms involved are yet to be elucidated.

Deciduosis in a cesarean scar.

Deciduosis is the presence of ectopic decidual tissue outside the uterus, pelvic, or abdominal organs usually associated with pregnancy. Cutaneous deciduosis is a highly uncommon manifestation of deciduosis and most commonly is misdiagnosed as a primary malignancy or a metastatic deposit. Typically, it is detected incidentally during operative procedures. It has been rarely documented within a surgical scar; with the incidence of surgically proven deciduosis being approximately 1.6%, and is often difficult to diagnose due to its rarity. Here, we present a case of deciduosis of cesarean scar in a 34-year-old pregnant female.

Evaluation of fertility and embryo implantation in rats after the oral administration of Salvia officinalis (sage) extract / Evaluación de la fertilidad y la implantación de embriones en ratas después de la administración oral de extracto de Salvia officinalis (salvia)

SUMMARY: In Saudi Arabia, it is widely believed that women with reproductive problems can use the extract of the sage plant as a tea drink. This study was conducted to investigate the effects of this herb on the fertility of female rats and embryo implantation. Forty-eight Wistar virgin female rats were divided into four groups at random, with 12 rats in each group. The control group received distilled water orally. The three treatment groups received different concentrations of sage extract: 15, 60, or 100 mg/kg for 14 days before mating, then mated with a male and sacrificed on the 7th day of gestation, the uterine horns removed, and photographed. The total body weight of mothers, weight of uteri and ovaries and number of fetuses were determined. Ovarian and uteri tissues were cut into 5 µ sections and stained with hematoxylin and eosin. Serum FSH, LH were determined by the ELISA method. The present study showed that low dose of sage (15 mg/kg) have no effects on serum concentration levels of FSH and LH hormones, also has no effect on the number of growing follicles. The present study showed a significant differences (P≤0.05) in body weight, ovary and uterus weight in the groups treated with high doses of Salvia officinalis as compared to control group. Also a significant differences (P≤0.05) found in FSH, LH hormones. Histological study showed overall histomorphological structural configurations including growing and matured graafian follicular countable changes, besides a number of corpora lutea and regressed follicles in the treated groups with high doses of Salvia officinalis as compared to control group. The researchers concluded that the extract of the sage plant with high doses can stimulate the growth graafian follicles and improve fertility in female rats.

RESUMEN: En Arabia Saudita, se cree ampliamente que las mujeres con problemas reproductivos pueden usar el extracto de la planta de salvia como bebida de té. Este estudio se realizó para investigar los efectos de esta hierba sobre la fertilidad de las ratas hembra y la implantación del embrión. Se dividieron cuarenta y ocho ratas hembra vírgenes Wistar en cuatro grupos al azar, con 12 ratas en cada grupo. El grupo control recibió agua destilada por vía oral. Los tres grupos de tratamiento recibieron diferentes concentraciones de extracto de salvia: 15, 60 o 100 mg/kg durante 14 días antes del apareamiento, luego se aparearon con un macho y se sacrificaron el día 7 de gestación, se extrajeron los cuernos uterinos y se fotografiaron. Se determinó el peso corporal total de las madres, el peso del útero y los ovarios y el número de fetos. Los tejidos ováricos y uterinos se cortaron en secciones de 5 µ y se tiñeron con hematoxilina y eosina. FSH sérica, LH se determinaron por el método ELISA. El presente estudio mostró que dosis bajas de salvia (15 mg/kg) no tienen efectos sobre los niveles de concentración sérica de las hormonas FSH y LH, tampoco tienen efecto sobre el número de folículos en crecimiento. El presente estudio mostró diferencias significativas (P≤0,05) en el peso corporal, peso de ovario y útero en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo control. También se encontraron diferencias significativas (P≤0,05) en las hormonas FSH, LH. El estudio histológico mostró configuraciones estructurales histomorfológicas generales que incluyen cambios contables en los folículos maduros (de Graaf) y en crecimiento, además de una cantidad de cuerpos lúteos y folículos en regresión en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo de control. Los investigadores concluyeron que el extracto de la planta de salvia en altas dosis puede estimular el crecimiento de los folículos maduros y mejorar la fertilidad en ratas hembra.

Deciduosis in a cesarean scar

ABSTRACT Deciduosis is the presence of ectopic decidual tissue outside the uterus, pelvic, or abdominal organs usually associated with pregnancy. Cutaneous deciduosis is a highly uncommon manifestation of deciduosis and most commonly is misdiagnosed as a primary malignancy or a metastatic deposit. Typically, it is detected incidentally during operative procedures. It has been rarely documented within a surgical scar; with the incidence of surgically proven deciduosis being approximately 1.6%, and is often difficult to diagnose due to its rarity. Here, we present a case of deciduosis of cesarean scar in a 34-year-old pregnant female.

Luteogenesis and Embryo Implantation Are Enhanced by Exogenous hCG in Goats Subjected to an Out-of-Season Fixed-Time Artificial Insemination Protocol.

The aim of this study was to evaluate the possible effect of two doses of hCG (100 and 300 IU) applied at two different times (7 and 14 d) after a fixed-time artificial insemination protocol (FTAI) upon some variables involved in the embryonic implantation rate in goats during the natural deep anestrous season (April, 25° north). The experimental units considered crossbred, multiparous, anovulatory goats (n = 69, Alpine, Saanen, Nubian x Criollo), with average body weight (43.6 ± 5.7 kg) and body condition score (1.86 ± 0.28 units) located in northern-semiarid Mexico (25° N, 103° W). Once the goat's anestrus status was confirmed, goats were subjected to an estrus induction protocol. Upon estrus induction confirmation, goats (n = 61) were subjected to a FTAI procedure. Immediately after the FTAI, the goats were randomly distributed to five experimental groups: (1). G100-7 (n = 13) 100 IU, hCG 7 d post-FTAI, (2). G100-14 (n = 12) 100 IU hCG, 14 d post-FTAI, (3). G300-7 (n = 12) 300 IU, hCG, 7 d post-FTAI, (4). G300-14 (n = 12) 300 IU hCG 14 d post-FTAI, and (5). Control group, CONT (n = 12) 0.5 mL saline, 7 and 14 d post-FTAI. The response variables conception rate (39.36 ± 0.23), fertility rate (27.96%), prolificacy rate (1.1 ± 0.29 kids), ovulation rate (0.74 ± 0.20 corpus luteum) corpus luteum diameter (10.15 ± 0.59 mm), embryo number (1.58 ± 0.20), and embryo implantation rate (48.96%), did not differ between treatments. However, while the variables fecundity rate (67%), embryo efficiency index-1 (33.99 ± 0.20%), and embryo efficiency index-2 (27.94 ± 0.30%) were favored by the G300-14 treatment, the corpus luteum area was favored (p < 0.05) by both G300-7 (113.30 ± 0.19 mm2) and G300-14 (103.04 ± 0.17 mm2). Such reproductive strategy emerges as an interesting approach, not only to enhance the out-of-season reproductive outcomes, but also to boost one of the main rulers defining the global reproductive efficiency of a heard, namely, the embryo implantation efficiency.

Adenomyosis and in vitro fertilization impacts - A literature review.

Adenomyosis is a gynecological condition, which is characterized by stromal and glandular endometrial tissue infiltration inti the myometrium, resulting in an increase of uterine volume. The etiology of adenomyosis is presently unknown, but some theories assist us in understanding its pathogenesis and natural history. Clinical manifestations are increased menstrual flow and dysmenorrhea, abnormal uterine bleeding, chronic pelvic pain, and dyspareunia. The signs and symptoms suggestive of adenomyosis are complemented by diagnostic methods such as transvaginal ultrasound (TVUS), ideally with intestinal preparation, magnetic resonance imaging (MRI) and surgery; although currently, there are no precise criteria for the classification of findings on imaging studies. The clinical and surgical therapeutic approach must be individualized, taking into account the patient's characteristics, for instance, age, parity, depth and number of adenomyotic foci, uterine volume and, mainly, clinical manifestations. A causal relation between adenomyosis and infertility has been repeatedly suggested, mostly due to the anatomo-physiopathological conditions originated by the adenomyosis on the female genital tract; however, definitive conclusions are still lacking. This pathology is found in approximately 25% of infertile women, especially those who have had recurrent pregnancy loss (RPL), recurrent implantation failure, older women seeking In Vitro fertilization (IVF) treatment, and those with concomitant endometriosis. To determine whether adenomyosis per se affects fertility, several researchers have focused on women who are affected by the condition and underwent IVF/intracytoplasmic sperm injection (ICSI); for this model provides more accurate data about the influence of adenomyosis on embryo implantation. Therefore, our objective was to analyze, through a systematic literature review, the effect of uterine adenomyosis on the probability of pregnancy by IVF / ICSI, as well as trying to point out the main difficulties and gaps to establish a standard protocol for the management of these patients, since most of the patients with adenomyosis have other associated gynecological pathologies, mostly endometriosis; in addition to the heterogeneity of the studies still remaining as an obstacle to precise conclusions.

Modifications of extracellular matrix features in the left and right uterine horns during the embryo pre-implantation period in Vicugna pacos.

More than 98% of the pregnancies in South American camelids is carried out in the left uterine horn (LUH). Hence, embryos originated from right-ovary ovulations have to migrate to the contralateral or left uterine horn (LUH) to implant and survive. A reason for this unique pattern of embryo implantation has not been elucidated yet. In general, embryo implantation involves an extensive extracellular matrix (ECM) remodeling within the endometrium, in which collagen and matrix metalloproteinases (MMPs) play an essential role. Deregulation of collagen and MMPs has been related to embryo implantation failure, miscarriage, and infertility. Therefore, we hypothesized that ECM components in camelids could be involved in differential embryo implantation and consequently the high incidence of left horn gestations. The aim of this study was to describe and compare changes in ECM components in the left and right uterine horn of non-pregnant and 15 days pregnant alpacas. To test this hypothesis, the collagen content was evaluated by specific staining with Picrosirius Red and using ImageJ 1.42q software. Subsequently, gene expression of the following components of the MMP pathway was determined: MMP-2, -3, -7, -9, and -14, MMP substrates (COL1A2 and COL3A1), MMP inhibitors (TIMP1 and TIMP2), LGMN, an MMP activator, and EMMPRIN, an extracellular matrix metalloproteinase inducer. Uterine horns of pregnant alpacas exhibited a marked decrease in collagen content. In contrast, transcript expression of COL1A2 and COL3A1 was higher in the LUH of pregnant alpacas. Gene expression of MMP-3, -7, -9, -14, LGMN, and EMMPRIN were also higher in the LUH of pregnant animals, whereas MMP-2 gene expression was higher in the LUH of both pregnant and non-pregnant alpacas. Expression of TIMP1 and TIMP2 increased during pregnancy, with higher values in the LUH. In conclusion, expression of ECM components displayed a specific pattern depending on the uterine side and the physiological status (pregnant vs non-pregnant) of the animal. The increased expression of ECM transcripts in the left uterine horn during early pregnancy in alpacas suggests the involvement of these molecules in a highly regulated process leading to the implantation process.

Conceptos básicos en inmunología de la reproducción: revisión narrativa de la bibliografía / Basic concepts in reproductive immunology: a narrative review of the literature

Resumen: ANTECEDENTES: La inmunología de la reproducción no es un área nueva: siempre ha estado relacionada con el aborto recurrente y con la falla repetida en la implantación, sobre todo en el contexto de una fertilización in vitro. Recientemente emergieron nuevos conceptos importantes que los ginecoobstetras deben considerar. OBJETIVO: Interrelacionar los conceptos básicos de inmunología, embriología y reproducción asistida para comprender mejor lo que la primera puede resolver y lo que no. METODOLOGÍA: Estudio retrospectivo efectuado con base en la búsqueda electrónica, llevada a cabo en febrero de 2020 en las bases de datos: PubMed y Google Scholar con los siguientes términos (MeSH): abortion, spontaneous/immunology; embryo implantation/immunology; HLA-c antigens/immunology; immune tolerance/immunology; immunity, maternally-acquired/immunology; uterus/immunology; killer cells, natural/immunology; placentation/immunology; receptors, kir/immunology; antigen presentation/genetics; antigen presentation/immunology; maternal-fetal exchange/genetics; maternal-fetal exchange/immunology. RESULTADOS: Se reunieron 289 artículos y se eliminaron 248 por no cumplir con los criterios de inclusión; solo se analizaron 41. Los artículos identificados sirvieron de base para actualizar la situación de la inmunología en el contexto de la medicina de la reproducción. Durante el proceso se revisaron otros artículos que sirvieran de soporte bibliográfico a los conceptos descritos en esta revisión. CONCLUSIONES: Debido al destacado interés en el estudio de la genética de los embriones, la medicina de la reproducción se enfocó más en ella y dejó de lado a la inmunología. Sin embargo, como la genética sigue sin poder explicar de manera adecuada las fallas en la implantación, la inmunología de la reproducción vuelve a cobrar impulso.

Abstract: BACKGROUND: Reproductive immunology is not a new area in reproductive medicine, it has always been related to recurrent miscarriage and repeated implantation failure, especially in the context of IVF. Recently, new concepts have emerged that are important for OBGYN specialists to keep in mind. OBJECTIVE: Interrelating the basic concepts of immunology, embryology and assisted reproduction to better understand what the former can and cannot solve. METHODOLOGY: Retrospective study based on the electronic search, carried out in February 2020, in the databases: PubMed and Google Scholar with the following terms (MeSH) The following MeSH terms were used: Abortion, Spontaneous/immunology; Embryo Implantation/immunology; HLA-C Antigens/immunology; Immune Tolerance/immunology; Immunity, Maternally-Acquired/immunology; Uterus/immunology; Killer Cells, Natural/immunology; Placentation/immunology; Receptors, KIR/immunology; Antigen Presentation/genetics; Antigen Presentation/immunology; Maternal-Fetal Exchange/genetics; Maternal-Fetal Exchange/immunology. RESULTS: 289 articles were collected, and 248 articles were deleted because they did not meet the inclusion criteria; only 41 were analyzed. The articles identified served as a basis for updating the status of immunology in the context of reproductive medicine. During the process, other articles were reviewed to serve as bibliographic support for the concepts described in this review. CONCLUSIONS: Due to the outstanding interest in the study of embryo genetics, reproductive medicine focused more on it and left immunology aside. However, since genetics still cannot adequately explain implantation failures, reproductive immunology is gaining momentum again.

Implantación embrionaria. Algunos aspectos moleculares en la receptividad endometrial. Revisión Bibliográfica / Embryonic implantation. Some molecular aspects in endometrial receptivity. Bibliographic review

RESUMEN La implantación embrionaria es un proceso que tiene lugar durante un breve periodo de tiempo donde el tejido endometrial alcanza un estado receptivo y donde se expresan moléculas que son necesarias para el proceso de implantación y posterior invasión del blastocisto. Este periodo se conoce como ventana de implantación y tiene lugar alrededor del día 20-21 del ciclo menstrual. El endometrio receptivo ha sido ampliamente estudiado desde el punto de vista histológico y molecular, y se conocen gran número de marcadores que forman parte de la firma molecular del endometrio receptivo, lo cual ha servido para desarrollar herramientas moleculares genómicas para el diagnóstico de la receptividad endometrial con utilidad clínica. Sin embargo, hasta ahora no se ha tenido en cuenta que la capacidad receptiva del endometrio tiene un componente inmunológico importante que facilita la entrada del tejido embrionario en el tejido materno. El objetivo de esta revisión es destacar ciertos grupos de biomarcadores identificados con un papel fundamental en el mecanismo de implantación.

ABSTRACT Embryo implantation is a process that takes place during a short period of time where the endometrial tissue reaches a receptive state and where molecules are expressed that are necessary for the implantation process and subsequent invasion of the blastocyst. This period is known as the window of implantation and takes place around day 20-21 of the menstrual cycle. The receptive endometrium has been widely studied from the histological and molecular point of view, and a large number of markers are known that are part of the molecular signature of the receptive endometrium, which has served to develop molecular genomic tools for the diagnosis of endometrial receptivity. with clinical utility. However, until now it has not been taken into account that the receptive capacity of the endometrium has an important immunological component that facilitates the entry of embryonic tissue into the maternal tissue. The objective of this review is to highlight certain groups of biomarkers identified with a fundamental role in the implementation mechanism.

Efecto en los resultados reproductivos con la "magnetic-actived cell sorting (MACS)" para la eliminación de espermatozoides positivos a anexina V en parejas con infertilidad inexplicable / Effect on reproductive outcomes by using "magnetic-actived cell sorting (MACS)" for the elimination of sperm-positive annexin-V in couples with unexplained infertility

Resumen Objetivo: Determinar si la eliminación de espermatozoides positivos a marcadores tempranos de apoptosis en parejas con infertilidad inexplicable incrementa la tasa de nacidos vivos. Materiales y métodos: Ensayo piloto, con asignación al azar, controlado y triple ciego; y un estudio paralelo de dos grupos. Se incluyeron parejas con diagnóstico de infertilidad inexplicable que se asignaron en una proporción 1:1 al grupo A (método de capacitación espermática swim-up) o grupo B (método de capacitación espermática swim-up complementado con separación magnética de células activadas; magnetic-actived cell sorting; MACS). Posteriormente, a todas las muestras se les efectuó una inyección intracitoplasmática de espermatozoides, como técnica de fertilización. Por último, todos los embriones obtenidos se analizaron hasta la etapa de blastocisto y todas las transferencias se llevaron a cabo en la misma etapa. Resultados: Se incluyeron 40 parejas y no se encontraron diferencias en la tasa de fertilización. Con la aplicación de MACS se obtiene mayor porcentaje de embriones de buena calidad en día 3 (90.3 vs 99.5%; p = 0.03) y en día 5 (77.3 vs 90.1%; p = < 0.0001) disminuyó el porcentaje de embriones arrestados (16.3 vs 7.9%; p = 0.01). Por último, las tasas de implantación (42.1 vs 57.1%), embarazo clínico (60 vs 80%) y nacidos vivos (55 vs 80%) aumentaron, sin diferencias estadísticamente significativas. Conclusiones: La separación magnética de células activadas (MACS) en parejas con infertilidad inexplicable mejora el desarrollo embrionario. A pesar de no existir una diferencia significativa se observa una tendencia al incremento de embarazos clínicos y nacidos vivos.

Abstract Objective: To determine if the live births delivery rate with the eliminating sperm positive to early apoptotic events is higher in couples with unexplained infertility. Materials and methods: A pilot randomized controlled trialA pilot and triple-blinded; using a parallel study of two groups. We included a total of 40 couples with unexplained infertility assigned in a 1:1 proportion either to the group A (sperm training method swim-up) or to the group B (swim-up sperm training method supplemented with the use of "magnetic-actived cell sorting (MACS)"). Subsequently, all samples were submitted to intracytoplasmic sperm injection as a fertilization technique. Finally, all embryos obtained were analyzed until the blastocyst stage, and all the transfers were performed in the same stage. Results: There are no differences in the fertilization rate; however, with the use of "magnetic-actived cell sorting" there is a higher percentage of good quality embryos on day 3 (90.3% vs 99.5%, p = 0.03) and day 5 (77.3% vs 90.1%, p = <0.0001). In addition, a decrease in the percentage of arrested embryos was demonstrated (16.3% vs 7.9%, p = 0.01). Finally, implantation (42.1% vs 57.1%), clinical pregnancy (60% vs 80%) and live birth rates (55% vs 80%) increased; however, no statistically significant differences were reported. Conclusions: The use of "magnetic-actived cell sorting" in couples with unexplained infertility improves embryonic development. Although there is no significant difference, a trend is observed in relation to the increase in the number of clinical pregnancies and live births.

The predictive value of serum concentrations of anti-Müllerian hormone for oocyte quality, fertilization, and implantation.

OBJECTIVE: This study aimed to identify a possible correlation between serum levels of anti-Müllerian hormone (AMH) and oocyte quality, embryo developmental competence, and implantation potential. METHODS: 4488 oocytes obtained from 408 patients undergoing ICSI cycles were evaluated. Oocyte dimorphisms, embryo quality on days two and three, blastocyst formation competence, fertilization rates, implantation rates, and pregnancy rates were correlated with serum levels of AMH using Pearson's correlation coefficient and regression analysis. RESULTS: A positive correlation was observed between serum levels of AMH and number of retrieved oocytes (CC: 0.600, p<0.001), fertilization rate (CC:0.595, p=0.048), and number of obtained embryos (CC:0.495, p<0.001). AMH did not affect the quality of cleavage stage embryos or the chance of blastocyst formation. However, AMH levels affected oocyte quality (OR:0.75, CI 0.44-0.96, p<0.001), and implantation (CC:0,116, p=0.031) and pregnancy (OR:1.22, CI:1.03-1.53, p<0.001) rates. CONCLUSION: Serum levels of AMH are a useful predictor of ovarian response to COS, oocyte quality, and fertilization. However, AMH levels may also compromise clinical outcomes; lower AMH levels did not impair embryo development.

Expression of PGR, HBEGF, ITGAV, ITGB3 and SPP1 genes in eutopic endometrium of infertile women with endometriosis during the implantation window: a pilot study.

OBJECTIVE: Alterations in endometrial receptivity may be involved in the etiopathogenesis of endometriosis-related infertility. The literature has suggested that patients with endometriosis present progestin resistance, which could affect embryo implantation. We question the presence of alterations in the expression of the progesterone receptor gene (PGR) and the genes related to endometrium-embryo interaction regulated by progesterone. This pilot study compared the expression of PGR, HBEGF, ITGAV, ITGB3, and SPP1 genes in eutopic endometrium during the implantation window (IW) in infertile women with endometriosis with that observed in the endometrium of fertile and infertile controls. METHODS: In this prospective case-control study, endometrial biopsies were performed during the IW in patients aged between 18 and 45 years old, with regular cycles and without endocrine/systemic dysfunctions, divided into endometriosis (END), infertile control (IC) and fertile control (FC) groups. Total RNA extraction, cDNA synthesis, and gene expression analysis by Real-Time PCR were performed. We assessed the size of the difference that our series was powered to detect. RESULTS: From the 687 patients who underwent diagnostic videolaparoscopy or tubal ligation at the University Hospital, 130 were eligible. Of these, 32 had endometrial samples collected, with 17 confirmed in the IW. Fifteen samples (5 END, 5 IC and 5 FC) were analyzed. There was no significant difference in the expression of any studied gene. Our sample size allowed us to identify or discard large differences (two standard deviations) among the groups. CONCLUSION: Endometriosis doesn't cause large changes in the endometrial expression of PGR, HBEGF, ITGAV, ITGB3 and SPP1 during the IW.

Live birth after transfer of vitrified-warmed embryo derived from vitrified-warmed oocyte and frozen-thawed sperm following failed ICSI: case report / Embarazo a partir de un embrión vitrificado derivado de oocitos vitrificados y espermios descongelados: reporte de un caso

Since the first successful pregnancy from a frozen human oocyte was reported, remarkable technological progress has been made in the area of cryopreservation of human oocytes. We report a successful delivery of two healthy babies after transfer of vitrified-warmed embryos derived from intracytoplasmic sperm injection (ICSI) with vitrified-warmed oocytes and frozen-thawed sperm. A female patient and her husband with severe oligoasthenspermia are reported. At the day of oocyte collection, very few inactive sperms were found in her husband semen. Multiple site open testicular biopsy was performed on her husband, but no sperm was retrieved. The patient did not become pregnant after transferring two embryos coming from half of oocytes and inactive sperms. The patient got pregnant and delivered two healthy babies after receiving a transfer of vitrified-warmed embryos from vitrified-warmed oocytes and frozen-thawed sperm.

La criopreservación de oocitos humanos ha progresado mucho desde que el primer embarazo exitoso desde un oocito congelado fue informado. Nosotros informamos el parto de dos bebés sanos después de transferir embriones vitrificados y recalentados y espermios descongelados. Se trata de una mujer y su marido con una oligoastenoespermia severa. En el día de la recolección de oocitos, se encontraron muy pocos espermios inactivos en el semen del marido. Se tomaron biopsias testiculares pero se encontraron muy pocos espermios inactivos. La mujer logró quedar embarazada y dio luz a dos bebés sanos después de recibir una trasferencia de embriones vitrificados y recalentados, y de espermios descongelados.

Recreational use of marijuana during pregnancy and negative gestational and fetal outcomes: An experimental study in mice.

The prevalence of marijuana use among pregnant women is high. However, the effects on gestation and fetal development are not well known. Epidemiological and experimental studies present conflicting results because of the route of administration, dose, time of exposure, species used, and how Cannabis toxicity is tested (prepared extracts, specific components, or by pyrolysis). In this study, we experimentally investigated the effects of maternal inhalation of Cannabis sativa smoke representing as nearly as possible real world conditions of human marijuana use. Pregnant mice (n=20) were exposed (nose-only) daily for 5min to marijuana smoke (0.2g of Cannabis) from gestational day (GD) 5.5 to GD17.5 or filtered air. Food intake and maternal weight gain were recorded. Ultrasound biomicroscopy was performed on 10.5 and 16.5dpc.On GD18.5, half of the dams were euthanized for the evaluation of term fetus, placenta, and resorptions. Gestation length, parturition, and neonatal outcomes were evaluated in the other half. Five minutes of daily (low dose) exposure during pregnancy resulted in reduced birthweight, and litter size was not altered; however, the number of male pups per litter was higher. Besides, placental wet weight was increased and fetal to placental weight ratio was decreased in male fetuses, showing a sex-specific effect. At the end of gestation, females from the Cannabis group presented reduced maternal net body weight gain, despite a slight increase in their daily food intake compared to the control group. In conclusion, our results indicate that smoking marijuana during pregnancy even at low doses can be embryotoxic and fetotoxic.

Is HLA-E a possible genetic marker relevant for natural conception?

BACKGROUND: HLA-E products, class Ib human leukocyte antigens, act in the immunology of human reproduction as modulators of the maternal immune system during pregnancy. AIMS: To evaluate HLA-E role in the establishment of a viable pregnancy. MATERIALS & METHODS: HLA-E was genotyped by sequence-based typing (SBT) and analyzed for specific polymorphisms, comparing couples who underwent assisted reproduction treatment (ART) and fertile control couples. RESULTS: There was a significant difference in HLA-E allele and genotype distributions between ART couples and control couples. The allele HLA-E*01:03 was observed in 63.2% of ART men and in 35.1% of fertile men (P = 0.0032). CONCLUSION: These results suggest that HLA-E allelic variants may play a role in the modulation of immune responses in the context of the inability of natural conception and establishment of a viable pregnancy.

Oocytes with smooth endoplasmic reticulum clusters originate blastocysts with impaired implantation potential.

OBJECTIVE: To study whether embryos derived from oocytes presenting a smooth endoplasmic reticulum cluster (SERC) are less likely to develop into blastocysts and implant. DESIGN: Transversal study. SETTING: Private university-affiliated in vitro fertilization (IVF) center. PATIENT(S): Total of 7,609 oocytes obtained from 743 intracytoplasmic sperm injection (ICSI) cycles. INTERVENTION(S): Oocytes split between the SERC-positive cycles (with at least one SERC-positive oocyte) and the SERC-negative cycles (only oocytes free of SERC). MAIN OUTCOME MEASURE(S): Embryo implantation. RESULT(S): A statistically significantly higher mean number of follicles (24.0 ± 10.5 vs. 19.6 ± 10.5), retrieved oocytes (17.8 ± 8.3 vs. 14.3 ± 8.0), and mature oocytes (13.5 ± 6.2 vs. 10.6 ± 5.9) were observed in the SERC-positive cycles as compared with SERC-negative cycles. The implantation rate was statistically significantly lower in SERC-positive cycles as compared with SERC-negative cycles (14.8% vs. 25.6%; odds ratio 0.61; 95% confidence interval, 0.44-0.86). When only cycles with in which none (0) or all the blastocysts transferred had implanted (100%) were analyzed, the mean implantation rate per transferred blastocyst in the SERC-negative group was 20.5%; no blastocysts derived from SERC-positive oocytes implanted. CONCLUSION(S): The occurrence of SERC impairs embryo implantation. Careful oocyte observation that takes into account the presence of SERC should be part of embryo selection strategy before transfer.

The Impact of Serum Progesterone Levels on the Results of In Vitro Fertilization Treatments: A Literature Review.

The aim of this review is to analyze the relationship between preovulatory progesterone (P) rise and in vitro fertilization (IVF) pregnancy outcomes. It also investigates the sources and effects of rises in progesterone levels, including the underlying mechanisms and potential strategies in preventing its elevation during ovarian stimulation. Progesterone is produced in the early follicular phase in the adrenal gland, which shifts toward the ovaries prior to ovulation. Several factors contribute to the etiology of P level increase including the number of multiple follicles, the overdose of gonadotropins and poor ovarian response. Nowadays, the influence of the preovulatory P rise on IVF outcome remains controversial. Several authors have failed to demonstrate any negative impact, while others reported a detrimental effect associated with the rise of P. It seems that P rise (1.5 ng/ml or 4.77 nmol/l) may have deleterious effects on endometrial receptivity, namely, accelerating the endometrial maturation process that subsequently narrows the period for implantation and thus decreases pregnancy rates. Recent studies have proposed different cutoffs according to the ovarian response, which may be a little high in patients with high response in relation to those of normal response or low response. To prevent a P rise, it might be preferable to use milder stimulation protocols, earlier trigger of ovulation, cryopreservation of all embryos and transfer in the natural cycle.

Resultados em ciclos de fertilização in vitro de acordo com a faixa etária feminina / Outcomes of in vitro fertilization cycles based on age groups

Como frutos da participação crescente da mulher como força de trabalho nas últimas décadas, o menor interesse pela maternidade1 e a tendência de postergá-la2 ocorrem apesar de haver diminuição progressiva do potencial reprodutivo feminino, mormente depois dos trinta anos de idade.3 Estimase que 75% das mulheres que iniciam tentativas deengravidar aos trinta anos etários darão à luz um nascido vivo dentro de doze meses, e apenas 44% o farão quando o início das tentativas ocorre aos quarenta anos de idade.4 Dados menos animadores registram declínio progressivo da fecundabilidade feminina com o avanço da idade, com taxas de gestação por ciclo fértil de 24%, 17%, 12% e 5% aos 25,30, 35 e 40 anos respectivamente.5Em estudo prévio, constatou-se interferência negativa significativa da idade da mulher sobre a resposta folicular ovariana e o número de oócitosmorfologicamente maduros obtidos em ciclos de fertilização in vitro com injeção intracitoplasmática de espermatozoides ou não,6 em concordância com outros estudos.2,3,7-10 Este estudo teve como objetivos comparar as taxas de gestação e a implantação em ciclos de fertilização in vitro com injeção intracitoplasmática de espermatozoide ou sem esta, de acordo com a classificação etária adotada pela Red Latinoamericana deReproducción Asistida,11 e aferir a capacidade da idade da mulher de predizer a ocorrência de gravidez clínica após ciclos terapêuticos.

Retrospective analysis of 216 in vitro fertilization cycles from January to December of 2010. Age groups were defined according to recommendations from the Red Latinoamericana de Reproducción Asistida: 34 years old or less, 35 to 39 years old and 40 years old or older. We evaluated the occurrence of clinical pregnancy (confirmed by transvaginal ultrasound in the fifth week after embryo transfer), embryo implantation and miscarriage rates. Areas below the curve (AUC-ROC) determined the ability of age to predict pregnancy after IVF/ICSI.