PURPOSE OF THE INVESTIGATION:To verify whether histologic confirmation of endometriosis impacts fertility outcomes.MATERIALS AND METHODS:Women with unexplained infertility (UI) underwent laparoscopic excision or ablation with CO2 laser or electrocautery of all suspected endometriotic lesions, followed by clinical treatment between January 2007 and December 2013; pregnancy (> 12 weeks) within 12 months of monitored cycles was the main outcome measured.RESULTS:Women with histological confirmation (n = 74) did not differ from those not confirmed (n = 29) with age, body mass index, gravidity, parity, ovulation induction protocol, and past duration of infertility. Pregnancy outcome was similar in both groups (39/74 vs. 15/29-p = 0.9--Chi-square) and there was no statistical difference in time to conceive/deliver (p = 0.7) between groups.CONCLUSIONS:There is no difference in fertility outcomes in women with UI, whether or not suspected endometriosis is confirmed pathologically.
Embryo grading is a mixture of subjective/objective assessments (e.g. cell stage/number; percent fragmentation) that has been minimally linked with implantation potential. Previously, we found that blastocyst ratios (length-width across the inner cell mass (ICM) axis) closely approximate phi (θ=1.618, AKA the Golden Mean or Ratio) in successful implantations (Roudebush et al., 2014). To further explore phi's potential in ART, this study calculated and compared ratios derived from ICM and total blastocyst areas of high quality classified embryos reported to have either successfully implanted or failed to implant. Retrospective post-transfer analysis of day-5 blastocyst (graded as high quality at time of embryo transfer) ICM and total area ratios were calculated for phi, and analyzed with pregnancy outcomes. Day-5 blastocyst stage embryo images, graded as being of high quality at the time of embryo transfer, were measured for ICM and total areas using tpsDIG2 software (life.bio. sunysb.edu/morph/). Area ratios were calculated. Receiver operator curve (ROC) and Student's t-test were used to assess to pregnancy outcomes. A total of 21 highly graded day-5 blastocysts were evaluated. Ratios ranged from a low of 0.822 (highly expanded) to a high of 2.086 (minimal expansion) with a mean of 1.272 (78.6% of the Golden Ratio). An ROC demonstrated a definitive phi cut-off value (i.e. criterion) for a viable pregnancy of 1.31: criterion >1.31, specificity 100.0, and sensitivity 71.4. With this criterion, pregnancy rates between the "implanted" phi group (>1.31 ng/mL; 90.9% pregnancy rate) and the "failed-to-implant" phi group (<1.31 ng/mL; 40.0% pregnancy rate) were significantly different (P < 0.001). Blastocyst stage embryo ratios (measured for ICM/total area) approximating phi were found to provide a more objective assessment of morphology than traditional approaches. Moreover, degree of blastocyst expansion appears to affect comparisons. While our initial data permit a calculated "cut-off value" or reference point, to achieve a viable pregnancy, this value does not include poor or low blastocyst grades. However, these results suggest calculating blastocyst area ratios relative to phi may assist in predicting pregnancy potential by offering a more objective means of selecting embryos at the time of transfer.
ObjectiveTo examine and compare cycle outcomes among patients demonstrating poor response to ovarian hyperstimulation that proceeded to oocyte retrieval to those that converted to intrauterine insemination (IUI).DesignCohort Study.Materials and MethodsComparison GroupsWomen demonstrating poor ovarian response while undergoing planned assisted reproductive technology (ART) cycles who proceeded to oocyte retrieval and In Vitro Fertilization (IVF)Women demonstrating poor ovarian response while undergoing planned ART cycles who converted to IUI.Inclusion Criteria-Cycle data from Greenville Health System REI Office, January 2004 - October 2013-Patients received gonadotropins as part of an ART cycle-Five or fewer follicles measuring greater than or equal to 15 mm in average diameter-Peak estradiol (E2) level less than 1000 pg/dL at time of human chorionic gonadotropin (hCG) trigger-Patients converted to IUI must have had at least one patent fallopian tube and were inseminated with a post-wash total motile sperm count >5 million/mL-Underwent standard stimulation protocolsExclusion Criteria-Sperm counts <5 million/mL for IUI group-Age <18 or >39-Bilateral tubal blockage for IUI groupPrimary Outcome: Live birthSecondary Outcome: Clinical pregnancyDemographics and Patient Information-Baseline FSH, Anti-Müllerian hormone, TSH, prolactin, DHEA-S-E2 levels at time of hCG trigger-Height & weight-Ethnicity-Age-Gravidity/Parity-Prior treatment.RESULTSAll data reported as either percentage frequency (n) or mean ± standard deviation. Statistical p-value based on either student t-test for continuous variables or chi-square/Fisher’s Exact test for categorical variables. P value <.05 considered statistically significant.Table 1Characteristics of Study ParticipantsCharacteristicIUI (N=29)IVF (N=48)P ValueBMI (kg/m2)23.9 ± 4.328.1 ± 7.20.01Age (yr)33.5 ± 3.933.7 ± 3.70.8Follicle countsBaseline Antral <15 mm11.1 ± 6.711.5 ± 6.40.8Baseline Antral ≥15 mm0.34 ± 1.90.04 ± 0.20.3After Hyperstimulation <15 mm7.9 ± 5.910.7 ± 7.40.09After Hyperstimulation ≥15 mm1.7 ± 1.23.4 ± 1.3<0.001Hormone LevelsE2 at trigger452.6 ± 250.2743.2 ± 181.8<0.001FSH8.7 ± 3.17.6 ± 2.70.12TSH2.0 ± 1.41.7 ± 1.00.32Prolactin11.3 ± 6.012.8 ± 12.50.56DHEA-S131.4 ± 62.5143.7 ± 124.90.62OutcomesClinical Pregnancy Rate7.0% (2)58.3% (28)<0.001Live Birth Rate0.0% (0)44.0% (21)<0.001 Open table in a new tab ConclusionThere was a clinically and statistically significant difference in both clinical pregnancy rate and live birth rate between groups. ObjectiveTo examine and compare cycle outcomes among patients demonstrating poor response to ovarian hyperstimulation that proceeded to oocyte retrieval to those that converted to intrauterine insemination (IUI). To examine and compare cycle outcomes among patients demonstrating poor response to ovarian hyperstimulation that proceeded to oocyte retrieval to those that converted to intrauterine insemination (IUI). DesignCohort Study. Cohort Study. Materials and MethodsComparison GroupsWomen demonstrating poor ovarian response while undergoing planned assisted reproductive technology (ART) cycles who proceeded to oocyte retrieval and In Vitro Fertilization (IVF)Women demonstrating poor ovarian response while undergoing planned ART cycles who converted to IUI.Inclusion Criteria-Cycle data from Greenville Health System REI Office, January 2004 - October 2013-Patients received gonadotropins as part of an ART cycle-Five or fewer follicles measuring greater than or equal to 15 mm in average diameter-Peak estradiol (E2) level less than 1000 pg/dL at time of human chorionic gonadotropin (hCG) trigger-Patients converted to IUI must have had at least one patent fallopian tube and were inseminated with a post-wash total motile sperm count >5 million/mL-Underwent standard stimulation protocolsExclusion Criteria-Sperm counts <5 million/mL for IUI group-Age <18 or >39-Bilateral tubal blockage for IUI groupPrimary Outcome: Live birthSecondary Outcome: Clinical pregnancyDemographics and Patient Information-Baseline FSH, Anti-Müllerian hormone, TSH, prolactin, DHEA-S-E2 levels at time of hCG trigger-Height & weight-Ethnicity-Age-Gravidity/Parity-Prior treatment. Comparison Groups Women demonstrating poor ovarian response while undergoing planned assisted reproductive technology (ART) cycles who proceeded to oocyte retrieval and In Vitro Fertilization (IVF) Women demonstrating poor ovarian response while undergoing planned ART cycles who converted to IUI. Inclusion Criteria -Cycle data from Greenville Health System REI Office, January 2004 - October 2013 -Patients received gonadotropins as part of an ART cycle -Five or fewer follicles measuring greater than or equal to 15 mm in average diameter -Peak estradiol (E2) level less than 1000 pg/dL at time of human chorionic gonadotropin (hCG) trigger -Patients converted to IUI must have had at least one patent fallopian tube and were inseminated with a post-wash total motile sperm count >5 million/mL -Underwent standard stimulation protocols Exclusion Criteria -Sperm counts <5 million/mL for IUI group -Age <18 or >39 -Bilateral tubal blockage for IUI group Primary Outcome: Live birth Secondary Outcome: Clinical pregnancy Demographics and Patient Information -Baseline FSH, Anti-Müllerian hormone, TSH, prolactin, DHEA-S -E2 levels at time of hCG trigger -Height & weight -Ethnicity -Age -Gravidity/Parity -Prior treatment. RESULTSAll data reported as either percentage frequency (n) or mean ± standard deviation. Statistical p-value based on either student t-test for continuous variables or chi-square/Fisher’s Exact test for categorical variables. P value <.05 considered statistically significant.Table 1Characteristics of Study ParticipantsCharacteristicIUI (N=29)IVF (N=48)P ValueBMI (kg/m2)23.9 ± 4.328.1 ± 7.20.01Age (yr)33.5 ± 3.933.7 ± 3.70.8Follicle countsBaseline Antral <15 mm11.1 ± 6.711.5 ± 6.40.8Baseline Antral ≥15 mm0.34 ± 1.90.04 ± 0.20.3After Hyperstimulation <15 mm7.9 ± 5.910.7 ± 7.40.09After Hyperstimulation ≥15 mm1.7 ± 1.23.4 ± 1.3<0.001Hormone LevelsE2 at trigger452.6 ± 250.2743.2 ± 181.8<0.001FSH8.7 ± 3.17.6 ± 2.70.12TSH2.0 ± 1.41.7 ± 1.00.32Prolactin11.3 ± 6.012.8 ± 12.50.56DHEA-S131.4 ± 62.5143.7 ± 124.90.62OutcomesClinical Pregnancy Rate7.0% (2)58.3% (28)<0.001Live Birth Rate0.0% (0)44.0% (21)<0.001 Open table in a new tab All data reported as either percentage frequency (n) or mean ± standard deviation. Statistical p-value based on either student t-test for continuous variables or chi-square/Fisher’s Exact test for categorical variables. P value <.05 considered statistically significant. ConclusionThere was a clinically and statistically significant difference in both clinical pregnancy rate and live birth rate between groups. There was a clinically and statistically significant difference in both clinical pregnancy rate and live birth rate between groups.
Anti-Mullerian hormone (AMH), a member of the transforming growth factor-β family, is produced in small amounts by ovarian granulosa cells after birth until menopause, and then becomes undetectable. AMH levels during the reproductive years are representative of the ovarian reserve and are useful to help determine egg recovery potential for ART. Whereas, AMH levels can reflect egg quantity, said levels have not been well correlated with pregnancy outcomes following IVF-ET. Therefore, the study objective characterized pregnancy outcomes by AMH levels in patients undergoing ART for infertility. Retrospective data analysis of patients undergoing IVF-ET at a tertiary fertility clinic. Patients diagnosed with polycystic ovarian syndrome (AMH > 5.0 ng/mL), ovarian insufficiency (AMH < 0.3 ng/mL), and male factor were excluded from the study. A receiver operator curve (ROC), and Student's t-test were used where appropriate and P was set at < 0.05. A total of 45 patients were included in this study. An ROC demonstrated a definitive AMH cut-off value (i.e. criterion) for a viable pregnancy of 1.26 ng/mL: criterion >1.26, specificity 65.2, and sensitivity 68.2. Using this criterion, pregnancy rates between the "good" AMH group (> 1.26 ng/mL; 65.2% pregnancy rate) and the "poor" AMH group (< 1.26 ng/mL; 27.3% pregnancy rate) was significantly different (P < 0.001). AMH has been shown to be a valid predictor of ovarian reserve, ovarian insufficiency and response to gonadotropin stimulation. Little information is available on the power of AMH to determine or predict pregnancy potential. While our initial data permit a calculated "cut-off value" or reference point, to achieve a viable pregnancy, this value does not exclude patients with low AMH a chance of obtaining a viable pregnancy. The AMH reference point may indicate that more aggressive means of fertility treatment would be warranted to obtain a viable pregnancy.
To determine the role of endometriosis in unexplained recurrent pregnancy loss (uRPL) and determine if luteal phase hCG support affects pregnancy loss rates. Retrospective cohort study. 209 consecutive patients with RPL (2 or more consecutive losses) age 40 and under were evaluated between January 2008 and December 2012. Patients underwent an evaluation including TSH, PRL, day 3 FSH and estradiol, testosterone and DHEA-S, hysterosalpingogram and/or sonohysterogram, lupus anticoagulant and anti-cardiolipin antibody. Explained recurrent pregnancy loss (eRPL) was categorized as structural abnormalities of the uterus, hormonal causes, autoimmune, or genetic. All monitored cycles were analyzed and recorded in our clinical database. The use of a single injection of human chorionic gonadotropin (hCG) for luteal phase support (250 ug Ovidrel or 5,000 units hCG) was compared to cycles without hCG support, in women with eRPL versus uRPL. Endometriosis was identified in a subset of patients in both groups and the finding of endometriosis was not used to exclude patients from either group. Patients were excluded if follow-up pregnancy data could not be verified. 94 patients had eRPL and 115 had uRPL. 41 patients in the eRPL group underwent treatment with hCG in the luteal phase of subsequent cycles. 75 patients in the uRPL group were similarly treated. Pregnancy rates in the eRPL and uRPL groups during hCG treatment cycles were 11.5% and 17.6%, respectively. Loss rates in those cycles were 3.8% for eRPL and 7.6% for uRPL. In addition, 49 eRPL and 93 uRPL patients underwent laparoscopy. Of these 19 (38.8%) explained and 38 (40.9%) unexplained RPL patients had endometriosis. hCG treatment in the luteal phase of RPL patients reduces the subsequent loss rate below what would be clinically expected based on prior publication. Endometriosis may be a contributing factor for RPL as it is found in approximately 40% of patients with a significant history of recurrent pregnancy loss.
ObjectivePolycystic ovary syndrome (PCOS) has long been known to be associated with poor reproductive outcomes, beyond simply ovulatory dysfunction. The purpose of this investigation was to determine the prevalence of endometriosis in women with PCOS and infertility and to determine the impact of surgical diagnosis and treatment on pregnancy rates in monitored cycles.DesignRetrospective observational study.Materials and MethodsOne hundred and fifty eight female subjects with infertility and PCOS according to the Rotterdam criteria were identified. Of 102 that underwent laparoscopy (L/S), any endometriosis found was staged and excised or ablated. Pregnancy rates were compared before and after L/S in all monitored cycles using Kaplan Meier Life Table analysis and Mantel-Cox test. Outcomes included the presence or absence of endometriosis, its classification and clinical pregnancy in monitored cycles.ResultsThere were no significant differences in age or BMI between pregnant and non-pregnant women or women that did or did not undergo L/S. Of 102 PCOS women that underwent L/S, 73 (71.5%) were found to have endometriosis (40% stage I, 41% stage II, 12% stage III, and 7% stage IV). In monitored cycles, PCOS women had a significantly shorter time to pregnancy and higher overall pregnancy rate if endometriosis was found and treated at surgery compared to those without a diagnosis of endometriosis (P=0.02).ConclusionA significant proportion of infertile women with PCOS may have unrecognized endometriosis, due to heavy menstruation and anovulatory bleeding. Laparoscopy significantly improves pregnancy outcomes in women with PCOS and endometriosis in monitored cycles, but women with PCOS that undergo L/S without findings of endometriosis had a worse prognosis, overall. When treating infertile women with PCOS, L/S should be considered when ovulatory cycles do not result in pregnancy. If endometriosis is not found at L/S, the prognosis appears poor for reasons that have yet to be determined. ObjectivePolycystic ovary syndrome (PCOS) has long been known to be associated with poor reproductive outcomes, beyond simply ovulatory dysfunction. The purpose of this investigation was to determine the prevalence of endometriosis in women with PCOS and infertility and to determine the impact of surgical diagnosis and treatment on pregnancy rates in monitored cycles. Polycystic ovary syndrome (PCOS) has long been known to be associated with poor reproductive outcomes, beyond simply ovulatory dysfunction. The purpose of this investigation was to determine the prevalence of endometriosis in women with PCOS and infertility and to determine the impact of surgical diagnosis and treatment on pregnancy rates in monitored cycles. DesignRetrospective observational study. Retrospective observational study. Materials and MethodsOne hundred and fifty eight female subjects with infertility and PCOS according to the Rotterdam criteria were identified. Of 102 that underwent laparoscopy (L/S), any endometriosis found was staged and excised or ablated. Pregnancy rates were compared before and after L/S in all monitored cycles using Kaplan Meier Life Table analysis and Mantel-Cox test. Outcomes included the presence or absence of endometriosis, its classification and clinical pregnancy in monitored cycles. One hundred and fifty eight female subjects with infertility and PCOS according to the Rotterdam criteria were identified. Of 102 that underwent laparoscopy (L/S), any endometriosis found was staged and excised or ablated. Pregnancy rates were compared before and after L/S in all monitored cycles using Kaplan Meier Life Table analysis and Mantel-Cox test. Outcomes included the presence or absence of endometriosis, its classification and clinical pregnancy in monitored cycles. ResultsThere were no significant differences in age or BMI between pregnant and non-pregnant women or women that did or did not undergo L/S. Of 102 PCOS women that underwent L/S, 73 (71.5%) were found to have endometriosis (40% stage I, 41% stage II, 12% stage III, and 7% stage IV). In monitored cycles, PCOS women had a significantly shorter time to pregnancy and higher overall pregnancy rate if endometriosis was found and treated at surgery compared to those without a diagnosis of endometriosis (P=0.02). There were no significant differences in age or BMI between pregnant and non-pregnant women or women that did or did not undergo L/S. Of 102 PCOS women that underwent L/S, 73 (71.5%) were found to have endometriosis (40% stage I, 41% stage II, 12% stage III, and 7% stage IV). In monitored cycles, PCOS women had a significantly shorter time to pregnancy and higher overall pregnancy rate if endometriosis was found and treated at surgery compared to those without a diagnosis of endometriosis (P=0.02). ConclusionA significant proportion of infertile women with PCOS may have unrecognized endometriosis, due to heavy menstruation and anovulatory bleeding. Laparoscopy significantly improves pregnancy outcomes in women with PCOS and endometriosis in monitored cycles, but women with PCOS that undergo L/S without findings of endometriosis had a worse prognosis, overall. When treating infertile women with PCOS, L/S should be considered when ovulatory cycles do not result in pregnancy. If endometriosis is not found at L/S, the prognosis appears poor for reasons that have yet to be determined. A significant proportion of infertile women with PCOS may have unrecognized endometriosis, due to heavy menstruation and anovulatory bleeding. Laparoscopy significantly improves pregnancy outcomes in women with PCOS and endometriosis in monitored cycles, but women with PCOS that undergo L/S without findings of endometriosis had a worse prognosis, overall. When treating infertile women with PCOS, L/S should be considered when ovulatory cycles do not result in pregnancy. If endometriosis is not found at L/S, the prognosis appears poor for reasons that have yet to be determined.
1. To develop an automated histological fibrosis quantification protocol. 2. To determine cardiac histologic injury in a transgenic mouse model of heart failure expressing a human mitochondrial progesterone receptor (PR-M). Transgenic mouse study. PR-M is mitochondrial progesterone receptor isoform that increases cellular respiration. An inducible (TET-On) transgenic mouse model expressing human PR-M under the control of the cardiac myosin heavy chain 6 promoter was developed. PR-M expression was induced with oral doxycycline followed in 2 wks by surgical constant thoracic aortic constriction (cTAC) to increase after-load. Intact male and ovariectomized female mice were treated with progesterone in oil (2.5 mg/day SQ) starting 1 wk prior to cTAC. Mice were sacrificed 8 wks after cTAC and cardiac PR-M expression determined with realtime RT-PCR. Cardiac fibrosis and capillaries were identified with Masson's trichrome and immunostaining with lectin respectively, by an investigator blinded to gene expression and treatment. Histologic images were acquired via digital slide scanning. Morphometrics were computed with ImageJ64 (NIH) and Photoshop CS5 (Adobe Systems). Data from the histologic quantification were analyzed with unpaired Student's t-test. Progesterone treated PR-M positive mice (N = 9) showed greater capillary density (P=0.04), greater capillary density to cardiomyocyte width ratio (P=0.02) and decreased cardiac fibrosis (P=0.03) after cTAC compared to progesterone treated PR-M negative mice (N = 17). The mean myocyte width was not different between the 2 groups (P=0.33). A novel computerized fibrosis quantification method for cardiac tissue was developed. Compared to controls, progesterone treated transgenic mice expressing a human mitochondrial progesterone receptor (PR-M) had fewer histologic signs of cardiac injury. These observations support a role for progesterone via a mitochondrial progesterone receptor in cardiac function.
To determine the effect on cardiac function of a human mitochondrial progesterone receptor (PR-M) using a transgenic mouse model of after-load induced heart failure. Transgenic mouse model An inducible (TET-On) transgenic mouse model was developed to express human PR-M under the control of the cardiac specific myosin heavy chain 6 promoter. PR-M expression was induced with oral administration of Doxycycline followed in 2 wks by surgical constant thoracic aortic constriction (cTAC) to increase after-load. Intact male and ovariectomized (OVX) female mice were treated with progesterone in oil (2.5 mg/day SQ) starting 1 week prior to cTAC. Echocardiograms were performed prior to and 2 and 4 wks after cTAC with determination of left ventricular dimensions and percent fractional shortening by an investigator blinded to the genotype and treatment. Cardiac parameters were compared with 2-way repeated measures ANOVA. Cardiac PR-M expression was determined by realtime RT-PCR. Male progesterone treated PR-M positive mice (N = 8) showed a significantly smaller left ventricular diameter (LVD) diastolic (mm) at 2 and 4 wks (3.3 vs 3.9 P<0.002, 3.5 vs 4.0 P<0.002), LVD systolic (1.2 vs 1.8 P<0.0001, 1.3 vs 2.0 P<0.0001) and a greater percent fractional shortening (64 vs 55% P<0.002, 62 vs 51% P<0.002) compared to progesterone treated PR-M negative mice (N = 12). Similar results were seen in comparison to other controls; vehicle treated PR-M positive (N = 9) and negative mice (N = 9). There was no difference in cardiac parameters between progesterone treated PR-M positive OVX females (N = 11) and progesterone treated PR-M negative OVX females (N = 22). Progesterone treatment via a human mitochondrial progesterone receptor (PR-M) decreases cardiac dysfunction in a transgenic male mouse model of heart failure. A lack of effect in ovariectomized females suggests a role for other sex steroids in this process.
The objective of this study was to examine endometrial L-selectin ligand as a potential marker of progesterone resistance in women with endometriosis. Prospective controlled study of endometrium and endometriotic tissues in a laboratory setting. Expression of L-selectin ligand was performed using MECA79 antibody in endometrium from normal women (n = 10) and women with endometriosis (n = 25) and compared to matched eutopic and ectopic endometrium from 10 women throughout the menstrual cycle. Xenografts of eutopic endometrium were implanted in subcutaneous pockets of ovexed immunodeficient RAG-2/gamma(c) mice, then treated with estradiol (E2) or E2 plus progesterone (P4) for a total of 22 days. At sacrifice the implants of endometrium were evaluated for L-selectin ligand expression. Regulation of the enzyme that regulates L-selectin ligand, N-acetylglucosamine-6-O-sulfotransferase (GlcNAc), was studied by RT-PCR in the hormone responsive endometrial cell line, ECC1. GlcNAc enzyme was stimulated by E2 and P4 treatment. Endometrium from normal women uniformly expressed the L-selectin ligand in the mid-secretory phase but was reduced in endometriosis patients with marked heterogeneity between patients (P=0.05). Ectopic endometrium showed a decline in L-selectin ligand expression (Fig. A). Human xenografts placed in RAG-2 gamma(c) mice expressed L-selectin in a P4 dependent manner and endometriosis endometrium lower expression and heterogeneity compared to normal endometrium (Fig. B). L-selectin ligand is regulated by P4 through modulation of Glc-NAc. Reduction in L-selectin ligand expression was noted in some women with endometriosis and in matched endometriotic implants. Human xenografts exhibited similar heterogenity in L-selectin ligand expression, suggesting that progesterone resistance may underly the altered endometrial protein expression patterns in some but not all women with this disorder.
To evaluate the pattern and intensity of the L-Selectin ligand in the endometrium from both fertile and infertile women throughout the menstrual cycle and during the window of implantation. This is a retrospective study on 48 endometrial samples from reproductive-aged women at various times in the menstrual cycle. Immunohistochemistry and western blot analysis was performed using the antibody, MECA-79, which recognizes the ligand for the L-selectin adhesion molecule. Endometrial biopsies were obtained from both fertile and infertile women during the menstrual cycle. Secretory phase samples were timed to the urinary LH surge. Overall, 48 samples were compared. Eighteen biopsies from normal cycling women included 3 proliferative, 3 early secretory (day15-19), 10 mid-secretory (day 20 to 24) and 2 late secretory phase (day 25-28). Additionally, mid-secretory samples were obtained from 7 women with PCOS in ovulatory cycles and 17 women with endometriosis, and 6 samples with significant histologic delay and luteal phase defect (LPD). These were compared to biopsies from normal fertile women in the mid-secretory phase. Statistical analysis was performed using ANOVA with Bonferroni correction with significance assigned at the 95% confidence interval (p < 0.05). The L-selectin ligand was absent during the proliferative phase and peaks during the early and mid-secretory phase in both glands (p=0.002 and 0.003) and lumen (p=0.004 and 0.005). In this first comparison of the L-selectin ligand in infertile and fertile women, we show that there was a slight decrease in overall expression of this antigen in glandular epithelium of women with PCOS and endometriosis (P =0.07 and P=0.052, respectively), compared to normal controls. However, in a subset of these patients the loss of L-selectin ligand was greater. A significant decrease was seen in the luminal expression in both PCOS and endometriosis patients (p=0.02 and p=0.048, respectively). Endometrium from women with LPD also had significantly less MECA79 staining on both glands (p=0.02) and lumen (p = 0.03), respectively. These findings were corroborated using western blot analysis. Given the suspected role in L-selectin as the attachment receptor for the human embryo, these results shed light on the maternal-fetal interface during the implantation window. The identification of depressed expression of luminal and glandular L-selectin ligand in a subset of women with PCOS and endometriosis provides further evidence for selective defects in endometrial receptivity in certain groups of women with infertility. The L-Selectin ligand is significantly reduced in some women with PCOS and endometriosis at the time of implantation. Further studies will be required to investigate the mechanism for this decrease, but evidence points to a reduction in the N-acetylglucosamine-6-O-sulfotransferase activity. Screening for such defects may be important prior to IVF or other infertility treatments.