Endometrial Environment Research Articles

Intrauterine administration of peripheral blood mononuclear cells enhances early development of the pre‐implantation bovine embryo

Intrauterine administration of peripheral blood mononuclear cells (PBMCs) prior to bovine embryo transfer (ET) was previously shown to improve the pregnancy rate. To better understand how PBMCs improve the pregnancy rate, we examined gene expression in the cells from uterine lumen and evaluated the morphology of bovine pre-attachment embryos in utero following intrauterine administration of PBMCs. On day 3 of the estrous cycle (day 0 = estrous), bovine PBMCs were isolated and suspended in RPMI 1640, and were incubated for 24 hr. The cultured PBMCs were administered non-surgically to the uterine horn ipsilateral to the corpus luteum on day 4 of the estrous cycle (PBMC group). On day 9, endometrial-luminal lymphoid cells from uterine lumen ipsilateral to the corpus luteum were collected by uterine flushing. Transcripts for macrophage-colony stimulating factor in the lymphoid cells were more abundant in the PBMC group than in the control group (P < 0.05). On day 7 (of the separate experiments), five blastocysts were each transferred to the luminal area, to which PBMCs had been administered on day 4. These embryos were allowed to develop in utero until day 15 of gestation, when embryos were non-surgically retrieved from the uterus. The average length of trophoblasts recovered from the PBMC group was significantly longer than that of the control group (51.6 ± 7.8 vs. 27.4 ± 6.0 mm, P < 0.05). Our results strongly suggest that intrauterine administration of PBMCs improves endometrial environment, which promotes early development of pre-attachment conceptuses.

Insulin resistance/hyperinsulinemia and reproductive disorders in infertile women.

Obesity, which disturbs lipid and glucose metabolism, is a recent medical concern. It threatens human health and also has adverse effects on reproductive functions by causing insulin resistance/hyperinsulinemia, especially in women with polycystic ovary syndrome (PCOS). For PCOS patients to prevent these adverse effects, it is important to take into account improving their lifestyles by exercise and proper diets. The relationship between insulin resistance/hyperinsulinemia and reproductive disorders should be understood as fully as possible in order to provide effective treatment. It is well known that insulin resistance and compensatory hyperinsulinemia can be triggered by obesity with visceral fat accumulation. Hyperinsulinemia affects granulosa cells in small follicles and theca cells. This condition induces early response to luteinizing hormones on granulosa cells of small follicles and causes premature differentiation of these cells, which eventually results in anovulation. For improvement of anovulation because of hyperinsulinemia, insulin-sensitizing agents (biguanide and thiazolidinedione derivatives) are useful. Hyperinsulinemia may adversely affect the endometrial functions and environment, and evoke implantation disturbance. Treatment with an insulin-sensitizing agent (metformin) improves the levels of glycodelin, insulin-like growth factor binding protein 1, and blood flow in spiral arteries during the peri-implantation period. It supports endometrial function, improves the endometrial environment, and facilitates embryo implantation. The rate of early pregnancy loss during the first trimester is 30-50% in women with PCOS, which is threefold higher than for normal women. Metformin treatment improves the levels of insulin, the homeostasis model assessment for insulin resistance, and plasminogen activator inhibitor activity, and decreases early pregnancy loss. It goes without saying that lifestyle change is fundamental for improving reproductive performance in addition to treatment with insulin-sensitizing agents.

In-vitro fertilization (IVF) outcomes in patients with hysteroscopic fibroid resection (SMR) or polypectomy

OBJECTIVE: To determine whether: 1. There is a difference in IVF outcome between patients who had an SMR or a polypectomy in the year prior to IVF and those who had no prior surgery; 2. The time interval between surgery and IVF impacts outcome. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: We stratified our sample into 3 groups: Those with an SMR in the prior year, those with a polypectomy, and those with no surgery. Groups were matched by age, parity, protocol, # of prior IVF cycles and mature oocytes. One-way ANOVA and Chi-square tests were used. We compared outcome between those who did IVF within 3 months of surgery and those who waited longer. Student's t-test was used. RESULTS: No significant difference in demographics, implantation (IR) or clinical pregnancy rates (PR) was seen among the 3 groups. Among those with an SMR, there was no significant difference in IR (20% vs 23%) or PR (36% vs 44%) between the two time intervals. Among those with a polypectomy, similar IR were seen between the two time intervals (23% vs 16%, p= 0.18). However, a trend towards greater PR was seen in the shorter interval group (45% vs 24%, p = 0.06).Tabled 1IVF Outcome by SurgerySMR (n=39)Polypectomy (n=54)No Surgery (n= 98)p valueAge (yrs)40.2 ± 2.940.1 ± 2.940.2 ± 0.70.9Protocol (% Luteal suppression)7474720.9# Prior IVF Cycles1.5 ± 1.91.2 ± 2.11.3 ± 1.60.8# Mature Oocytes8.82 ± 4.68.24 ± 4.47.82 ± 5.00.5IR0.22 ± 0.30.20 ± 0.30.17 ± 0.30.5PR0.41 ± 0.50.35 ± 0.50.31 ± 0.50.5M ± SD. Open table in a new tab M ± SD. CONCLUSION: IVF soon after hysteroscopic surgery does not appear to negatively affect outcome. The trend towards increased PR in those who did IVF within 3 months of their polypectomy might be due to an initial benefit of the procedure or from a residual effect of altering the endometrial environment. Further investigation of the impact of intra-uterine surgery on IVF outcome is warranted.

Evidence-Based Management of Infertile Couples with Repeated Implantation Failure Following IVF

Embryo implantation depends on both embryo quality and the endometrial environment. Implantation failure has a complex, variable pathophysiology and is detrimental to the outcome of in vitro fertilization (IVF). Thus, patients with multiple implantation failure require an individualized approach to diagnosing and managing treatment options for future IVF cycles. These options should be based on concrete, unambiguous, consistent scientific evidence with random- ized, controlled trials. We review and discuss 14 treatment options: (i) blastocyst transfer, (ii) assisted hatching, (iii) co-culture, (iv) preimplanta- tion genetic screening, (v) hysteroscopy, (vi) sildenafil, (vii) salpingectomy for tubal disease, (viii) oocyte donation, (ix) transfer of six or more embryos, (x), intratubal embryo transfer, (xi) natural cycle IVF, (xii) antiphospholipid antibodies (APA) testing and treatment, (xiii) allogenic lymphocyte therapy, and (xiv) IV immunoglobin therapy. The approaches were evaluated based on available information from studies, expert opinions, consensus, etc. We conclude that blastocyst transfer, assisted hatching, salpingectomy for tubal disease, and hysteroscopy in IVF procedures are clinically effective. This review serves as a summary of current treatment options for clinicians to counsel patients and manage their expectations based on strong and reliable evidence.

Ovarian stimulation retards postimplantation development and alters global gene expression profile of blastocysts in mouse

This study compares the quality, developmental capacity and global gene expression profile of embryos generated from superovulated and natural cycles. We found that ovarian stimulation impaired quality of blastocysts (cell number: 68.9 +/- 6.9 vs. 76.8 +/- 7.9; diameter of blastocysts: 145.3 +/- 76.9 microm vs. 152.6 +/- 65.5 microm), fetus development (rate of development to term: 45.5% vs. 69.1%; weight of 18.5-dpc fetuses: 1.23 +/- 0.03 g vs. 1.34 +/- 0.03 g) and caused 92 genes differentially expressed.

Progesterone in pregnancy; receptor–ligand interaction and signaling pathways

Progesterone is indispensable in creating a suitable endometrial environment for implantation, and also for the maintenance of pregnancy. Successful pregnancy depends on an appropriate maternal immune response to the fetus. Along with its endocrine effects, progesterone also acts as an "immunosteroid", by contributing to the establishment of a pregnancy protective immune milieu. Progesterone plays a role in uterine homing of NK cells and upregulates HLA-G gene expression, the ligand for NK inhibitory and activating receptors. At high concentrations, progesterone is a potent inducer of Th2-type cytokines as well as of LIF and M-CSF production by T cells. A protein called progesterone-induced blocking factor (PIBF), by inducing a Th2-dominant cytokine production mediates the immunological effects of progesterone. PIBF binds to a novel type of the IL-4 receptor and signals via the Jak/STAT pathway, to induce a number of genes, that not only affect the immune response, but might also play a role in trophoblast invasiveness.

The preconceptional endometrial environment affects both implantation and gestation in human

The preconceptional endometrial environment affects both implantation and gestation in human

Evidence for Estrogen-Dependent Uterine Serpin (SERPINA14) Expression During Estrus in the Bovine Endometrial Glandular Epithelium and Lumen1

Uterine secretions have a dominant impact on the environment in which embryo development takes place. The uterine serpins (SERPINA14, previously known as UTMP) are found most abundantly during pregnancy in the uterus of ruminants. Although progesterone is currently assumed to be the major regulator of SERPINA14 expression, our recent study of transcriptome changes in bovine endometrium during the estrous cycle unexpectedly detected a marked upregulation of SERPINA14 mRNA levels at estrus. The present study describes the full-length mRNA sequence, genomic organization, and putative promoter elements of the SERPINA14 gene. The SERPINA14 mRNA abundance was quantified by real-time RT-PCR in intercaruncular endometrium at several time points during the estrous cycle and early pregnancy. Highest levels were found at estrus, followed by a dramatic decrease and a moderate expression during the luteal phase. Transcript levels were higher in pregnant endometrium compared with controls at Day 18. At estrus, immunoreactive protein was localized in deep glandular epithelium, and Western blotting concomitantly showed the 52-kDa form in uterine flushings. SERPINA14 mRNA was significantly upregulated in glandular endometrial cells in vitro after stimulation with estradiol-17beta and progesterone, but not after interferon-tau treatment. Our results clearly demonstrate that SERPINA14 appears distinctly in bovine endometrium during the estrus phase. A supporting role toward providing a well-prepared endometrial environment for passing gametes, especially sperm, is assumed.

The effect of hyperstimulation on transforming growth factor β 1 and β 2 in the rat uterus: possible consequences for embryo implantation

To investigate the effect of exogenous gonadotropins on the expression of transforming growth factor (TGF) beta(1) and beta(2) in the rat uterus and its consequences for successful embryo implantation. Controlled experimental research study. School of Anatomical Sciences, University of the Witwatersrand. Thirty-six adult, virgin, female Sprague-Dawley rats and two fertile males. Follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG) were superimposed upon the normal hormonal milieu of normal, cycling female rats before mating. Uterine tissue was collected at peri-implantation stages (i.e., at 4.5, 5.5, and 6.5 days) after mating. Enzyme-linked immunosorbent assay (ELISA) was performed to estimate the blood estrogen and progesterone levels, and immunohistochemistry was performed to localize the TGF-beta(1) and TGF-beta(2) in the uterus. Hyperstimulation affecting the expression of both TGF-beta(1) and TGF-beta(2) during the peri-implantation period. The release of ovarian steroids was altered, causing a change in the endogenous hormonal environment. A marked increase in the expression of TGF-beta(2) was distinct in the glandular epithelium. Expression of both TGF-beta(1) and TGF-beta(2) was weaker in the subluminal stroma when compared with the deeper stromal region. Hyperstimulation with exogenous hormones affects the expression of both TGF-beta(1) and TGF-beta(2), which may contribute to the disruption of the endometrial environment required for successful embryo implantation.

Induction of early decidualization by cadmium, a major contaminant of cigarette smoke

To investigate the effect of cadmium (Cd) contamination on endometrial function, human endometrial stromal cells were isolated and cultured with E(2) plus P in the presence of Cd, a major contaminant in cigarette smoke, and assayed for PRL concentrations and its messenger RNA expression. Cd significantly increased PRL concentrations in the culture media and significantly up-regulated PRL messenger RNA expression of the endometrial stromal cells, suggesting that Cd stimulates decidualization of the endometrium and may disrupt endometrial environment, causing early decidualization.

IL-1β-induced pro-inflammatory chemokines is altered by atorvastatin and doxycycline treatment of human endometrial cells

OBJECTIVE: Endometrial environment during breakthrough bleeding is characterized by inflammatory reaction and increased production of proinflammatory mediators. Since HMG-CoA reductase inhibitors (statins) and doxycycline (DOX) have been shown to have anti-inflammatory properties, we investigated whether IL-1β-induced proinflammatory chemokines are altered by statin as compared to Dox treatment of the endometrial cells.

Progestagen therapy for recurrent miscarriage

Recurrent pregnancy loss (RM) affects 0.5-1% of couples. The pathophysiology of RM is complex. The suggested causes include anatomical, genetic and molecular abnormalities, endocrine disorders, thrombophilias and anti-phospholipid syndrome. In approximately 50% of the cases neither of the above can be identified. We aimed at examining the evidence on the role of progesterone in the pathophysiology of RM, and the clinical evidence on effectiveness of progestogen treatment. We searched PubMed and the Cochrane database covering the period of 1968-2007. The search terms progestogens and recurrent miscarriage, NK cells and recurrent miscarriage as well as cytokines and recurrent miscarriage were used. Progesterone is indispensable for creating a suitable endometrial environment for implantation. RM may be due to subnormal progesterone secretion and retarded endometrial development in the peri-implantation period. Progesterone also acts on the immune system, mainly by affecting cytokine synthesis and the function of NK cells. A recent meta-analysis showed that though progesterone treatment did not affect pregnancy outcome in women with miscarriages in general, separate analysis of three small and dated studies including altogether 91 patients with RM revealed a small but significant effect. It is noteworthy that the design of these 40 years old studies does not meet modern requirements. Standardized laboratory protocols for identifying potential targets of progestogen treatment as well as implementation of well-designed randomized studies are needed to establish the usefulness of progesterone supplementation in the treatment of RM.

CDB-2914, a novel selective progesterone receptor modulator, differentially regulates endometrial gene expression in the proliferative phase of the menstrual cycle

In response to ovarian steroids, human uterine endometrium dynamically alters its composition throughout the menstrual cycle. As part of a blinded, randomized, placebo-controlled trial, CDB-2914 (CDB), a selective progesterone modulator, was used to treat women with symptomatic uterine leiomyomas over a 90 day period. CDB induced amenorrhea in all treated patients. The objective of this study was to evaluate effects of CDB and placebo on the endometrial molecular environment and to identify possible mechanisms responsible for differential actions.

Spontaneous abortion in donor oocyte recipients: the risk associated with extremes of body mass

The oocyte donation model distinguishes between those factors that affect reproductive function at the level of the oocyte and those that affect the endometrial environment. Studying the impact of body mass index (BMI) on pregnancy outcomes in oocyte recipients removes dysfunction in ovarian follicular maturation that might be caused by the recipient's abnormal body mass. Instead, the potential role of body mass on endometrial receptivity is isolated and evaluated. Retrospective analysis. 315 donor oocyte recipient cycles from 2004–2007 were analyzed. Exclusion criteria included no embryo transfer, therapeutic termination, or incomplete cycle information. In order to eliminate over-representation of patients with failed cycles, only the earliest cycle for each recipient was included. Patients were stratified into four groups based on BMI: underweight (<20 kg/m2), normal weight (20–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2). Pregnancy rates, clinical pregnancy rates, spontaneous abortion rates, and early pregnancy loss rates were compared among patients in the four BMI groups. When underweight, overweight, and obese patients were compared to normal weight patients, no significant differences were observed in pregnancy rate, clinical pregnancy rate, spontaneous abortion rate, or pregnancy loss rate. However, patients at the extremes of body mass index, either underweight (<20 kg/m2) or obese (≥30 kg/m2), were at increased risk of spontaneous abortion when compared to patients in the central range of BMI (13.2% vs. 5.9%, P=0.037).TablePregnancy outcomes by BMI in donor oocyte recipientsUnderweightNormal weightOverweightObeseNumber of patients521786124Pregnancy rate67.3%63.5%57.4%54.2%Clinical pregnancy rate59.6%57.3%47.5%45.8%Spontaneous abortion rate13.5%6.7%3.3%12.5%Pregnancy loss rate21.2%12.9%13.1%20.8% Open table in a new tab Oocyte donation recipients at the extremes of body mass index are at significantly increased risk of spontaneous abortion when compared with average weight patients. The increase in spontaneous abortions observed at the extremes of body mass suggests a potential shared etiology for endometrial dysfunction related to body mass. It also provides useful information for counselling patients about optimizing reproductive outcome by normalizing body mass prior to an oocyte donation cycle.

Immune parameters in mares resistant and susceptible to persistent post-breeding endometritis: Effects of immunomodulation

Our objective was to characterize immune parameters in susceptible (SM) and resistant (RM) mares, with and without artificial insemination (AI) and immunomodulation. Eight RM and eight SM were selected based on their reproductive history and functional tests. Both groups of mares were evaluated during three consecutive cycles: Cycle 1, untreated cycle (control); Cycle 2, AI with dead semen; Cycle 3, AI with dead semen and immunomodulation. Endometrial biopsies were taken during the three cycles as follows: Cycle 1—at estrus, when follicles ≥35 mm and at diestrus (7 ± 1 days after ovulation); Cycle 2—at estrus 24 h post-AI, and at diestrus; Cycle 3—at estrus 24 h after treatment with a Mycobacterium phlei cell-wall extract (MCWE) and AI, and at diestrus. The mRNA transcription (mRNAT) of IL-8 and IL-10 were determined by real-time PCR. Image analysis of immunonhistochemistry slides was performed using digital software (Image-Pro Plus v 5.0; Media Cybernetics); the percentage of stained area was determined for Mayor Histocompatibility Complex II (MHC-II), polymorphonuclear leukocytes (PMN) and T lymphocytes (TL) on each tissue section. In Cycle 1, SM had significantly higher MHC-II, TL, PMN and IL-8 than RM during estrus ( P < 0.006, P < 0.0005, P < 0.05, respectively), while transcription of IL-10 was significantly lower than in RM ( P < 0.0001). During diestrus, SM had higher levels of TL, PMN and IL-8 than RM ( P < 0.0001). After AI (Cycle 2), SM had higher levels of IL-8 and lower levels of IL-10 than RM at estrus and no differences were detected for MHC-II, TL and PMN positive cells. During diestrus in the same cycle, all the immune parameters were higher in SM mares ( P < 0.005, P < 0.0004, P < 0.0001, P < 0.02, respectively). When MCWE was applied at the time of AI (Cycle 3), SM expressed significant higher levels of IL-10 24 h after treatment ( P < 0.005), which were also higher than in the control Cycle 2 or after AI (Cycle 2). However, no significant differences were detected for MHC-II, lymphocytes-PMN or IL-8 between SM and RM during diestrus in Cycle 3. This study showed that SM had higher levels of all immune parameters except IL-10 than RM during Cycle 1. After AI (Cycle 2), the inflammatory condition persisted in SM but not RM mares until day 7 post-ovulation. Following treatment with MCWE at the time of AI (Cycle 3) uterine immunological changes in SM resulted in an endometrial immune environment similar to that found in normal RM.

The Altered Distribution of the Steroid Hormone Receptors and the Chaperone Immunophilin FKBP52 in a Baboon Model of Endometriosis Is Associated With Progesterone Resistance During the Window of Uterine Receptivity

This study examines the distribution of estrogen receptors (ESR), progesterone receptors (Pgr), and the chaperone immunophilin FKBP52 in the eutopic endometrium in a baboon model of endometriosis during the window of receptivity to determine if their aberrant distribution contributes to reduced fecundity. Endometriosis was induced by inoculation of menstrual endometrium into the peritoneal cavity. Eutopic endometrium was collected at 3, 6, 9, 12, and 15 months postinoculation. Western blot (WB) and immunohistochemical analyses were performed. Isolated endometrial stromal cells were cultured in the presence or absence of steroid hormones. In animals with endometriosis, ESR-1 (ER-alpha) decreased in endometrial stromal cells, while ESR-2 (ER-beta) was reduced in both glandular epithelial (GE) and stromal cells. Immunoreactive total Pgr was markedly diminished in the GE, which was confirmed by WB analysis. Furthermore, treatment of isolated stromal cells from baboons with endometriosis with hormones did not increase levels of PRA or PRB as in control baboons. FKBP52 was also reduced in the eutopic endometrium of baboons with endometriosis. Endometriosis results in an aberrant distribution of ESR-1, ESR-2, Pgr, and FKBP52 in the eutopic endometrium. The authors propose that a dysregulation in the paracrine signaling between the endometrial stromal and GE cells reduces the responsiveness of Pgr, creating an endometrial environment that is unsuitable for implantation.

The antifertility effectiveness of copper/low-density polyethylene nanocomposite and its influence on the endometrial environment in rats

Purpose The study was conducted to investigate the antifertility effectiveness of copper/low-density polyethylene nanocomposite (nano-Cu/LDPE) and its influence on the endometrial environment in rats. Methods One hundred and seventy sexually mature female Sprague–Dawley (SD) rats were randomly divided into five groups: sham-operated control group (SO group, n=10), bulk copper group (Cu group, n=40), LDPE group ( n=40), and nano-Cu/LDPE groups I ( n=40) and II ( n=40). Twenty rats in each group except for the SO group were mated with male rats of proven fertility, from 30 days after insertion, and the antifertility rates (ATs) were observed at Day 11 of pregnancy. The concentrations of prostaglandin E 2 (PGE 2) and tissue plasminogen activator (tPA) in the endometrium of the remaining rats in each group were measured by using ELISA at the 30th and 60th day after insertion, respectively. Results ATs in the Cu group and nano-Cu/LDPE groups I and II (100%) were significantly higher than those in the LDPE group (p<.05). Compared with those in the SO group, the concentrations of PGE 2 and tPA in all experimental groups except for PGE 2 levels in the LDPE group were significantly increased at Day 30 after insertion, and these parameters in the nano-Cu/LDPE groups were significantly lower than in the Cu group (p<.05). At Day 60 after insertion, tPA levels were still higher in the Cu and nano-Cu/LDPE groups, but there was no difference in PGE 2 levels in all groups except for the Cu group. Conclusion Nano-Cu/LDPE exhibits satisfactory contraceptive efficacy with less influence on the endometrium PGE 2 and tPA levels.

Doxycycline alters the expression of inflammatory and immune-related cytokines and chemokines in human endometrial cells: implication in irregular uterine bleeding*

Increased production of pro-inflammatory mediators is considered central in the manifestation of events leading to irregular uterine bleeding in progestin-only contraceptive users. Evidence suggests that in addition to its antimicrobial property, doxycycline (Dox) acts as an anti-inflammatory agent mainly through the suppression of pro-inflammatory mediators. We tested this hypothesis in the endometrial environment using an in vitro model consisting of isolated human endometrial glandular epithelial and stromal cells and a human endometrial surface (HES) epithelial cell line cultured under defined conditions. We found that Dox at doses ranging from 1 to 100 microg/ml had a limited growth-inhibitory effect on these cells, whereas Dox in a dose-dependent manner inhibited the production of tumour necrosis factor-alpha (TNF-alpha). Using multiplex cytokine/chemokine protein analysis to test a broader range of Dox activity, we found that Dox at 25 microg/ml either alone or in the presence of 17beta-estradiol (E2), medroxyprogesterone acetate (MPA) and E2+MPA (10(-8) M) as well as TNF-alpha (25 ng/ml), representing the endometrial environment exposed to contraceptives as well as inflammatory conditions, respectively, altered the production of multiple cytokines and chemokines as compared with untreated controls. These actions of Dox occurred in cell-, ovarian steroid- and cytokine/chemokine-dependent manners. Although Dox reduced the regulatory action of steroids on the production of these cytokines/chemokines, it was less effective on TNF-alpha-treated cells. The results support the hypothesis that Dox, by modulating the endometrial expression of multiple inflammatory-related cytokines/chemokines in a cell- and cytokine/chemokine-dependent manner, may have a therapeutic potential in patients experiencing irregular uterine bleeding, in particular in progestin-dominant contraceptive users.

Nacimiento a partir de Fertilización IN VITRO en ciclo natural

El ciclo natural combinado con fertilización in vitro (FIV) y transferencia embrionaria está mostrando ser una opción de gran beneficio especialmente para pacientes mayores de 35 años, ya que se disminuye el costo del tratamiento por la facilidad de no utilizar hormonas para estimulación ovárica y por tanto se elimina el riesgo de la utilización de hormonas exógenas, con el beneficio adicional de transferir los embriones obtenidos en un ambiente endometrial libre del efecto de la estimulación.Objetivo: describir el embarazo y nacimiento de un niño sano como resultado de fertilizacion in vitro en un ciclo menstrual normal sin utilización de estimulación exógena de gonadotropinas.Procedimiento: se realizó seguimiento folicular por ecografía a una paciente con factor tuboperitoneal, hasta que el folículo dominante alcanzó un tamaño de 16 mm y grosor endometrial mayor de 14 mm. Se aplicaron 10.000 UI de hCG y 36 horas después se realizó aspiración folicular. El folículo dominante con un oocito en metafase II (MII), se fertilizó por ICSI y a las 48 horas de cultivo, el embrión obtenido fue transferido al útero previa preparación endometrial.Resultados: se obtuvo un óvulo en MII, el cual fertilizó después de ICSI y se transfirió un embrión en 4 blastómeras grado I a las 48 h de la aspiración. Doce días después de la transferencia embrionaria se realiza prueba de embarazo cuantitativa con un resultado positivo y nacimiento de un bebé sano.Conclusiones: la obtención de un óvulo maduro sin estímulo hormonal y transferencia embrionaria en ciclo natural, ofrece una nueva alternativa al tratamiento de infertilidad independiente de la edad.

The Estrogen Early Response Gene FOS Is Altered in a Baboon Model of Endometriosis1

Endometriosis, the presence of a functional endometrium outside of the uterine cavity, is associated with infertility. In our simulated model of pregnancy in baboons with experimental endometriosis, hCG infusion fails to induce expression of the immunoregulatory protein glycodelin. To test the hypothesis that the development of endometriosis is associated with an aberrant endometrial immunological environment, we examined the expression of a series of immunoregulatory genes in endometrium from baboons with and without endometriosis. Six months following intraperitoneal inoculation with menstrual endometrium, eutopic endometrium was surgically collected between Days 9 and 11 postovulation. Control endometrium was similarly collected from disease-free animals. Total RNA was extracted, and biotinylated cDNA probes were hybridized to the SuperArray GEArray Q series Th1/Th2/Th3 cDNA array, representing 96 genes. Gene expression levels were determined using ScanAlyze and GEArray Analyzer software. Seven genes were upregulated, including JUND, FOS, CCL11, NFKB1 and others, in the endometrium from baboons with endometriosis compared with the endometrium from disease-free animals; one gene, IL1R1, was downregulated. Quantitative RT-PCR confirmed upregulation of FOS and CCL11 in endometriotic eutopic endometrium. Immunohistochemical analysis revealed altered levels and distribution of FOS protein in the eutopic endometrium of baboons with induced endometriosis. These data suggest that in an induced model of endometriosis an aberrant eutopic immunological environment results in a decreased apoptotic potential and in rapid alterations in endometrial gene expression. We propose that the reduced fecundity associated with endometriosis has a multifold etiology in spontaneous and induced disease.