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ABSTRACT: Increasing evidence supports the involvement of complex antibody-mediated immunologic events at the decidua-trophoblast interface. Our objective is to define the humoral immune responses of pregnant women with a history of recurrent pregnancy loss (RPL) compared with gestation-age-matched and non-pregnant controls in terms of trophoblast-derived antigenic targets and IgG subclasses.
Immunoprecipitation and Western immunoblotting were performed to characterize IgG subclass reactivity to Sw.71 trophoblast-derived fetal fibronectin and alpha-2-macroglobulin, using serum obtained from first-trimester pregnant RPL subjects, gestation-age-matched controls, and non-pregnant controls.
Using a generalized linear model, sera from women with a history of RPL exhibited increased IgG(3) immunoreactivity to trophoblast-derived fetal fibronectin and alpha-2-macroglobulin compared with controls (P < 0.001 and P < 0.001, respectively).
IgG(3) reactivity in women with RPL may play a significant role in aberrant immune-regulatory mechanisms in early pregnancy. Further investigations into the role of autoantibodies against trophoblast-derived proteins in implantation and pregnancy are warranted.
American Journal Of Reproductive Immunology 08/2012; 68(5):438-49. · 2.17 Impact Factor
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ABSTRACT: To evaluate the scientific literature on current methods of uterine cavity and tubal patency assessment.
Review of literature and appraisal of relevant articles using MEDLINE, OVID, EMBASE, and Cochrane on-line databases.
Current pelvic imaging subfertility investigations are compared with the gold standard laparoscopy. The technical aspects, associated risks, potential advantages, and weighted utility of each screening study are discussed. A comprehensive analysis of the clinical evidence regarding the safety, tolerance, and accuracy of hysterosalpingo-contrast sonography compared with alternative screening studies and/or laparoscopy is reviewed.
Increasing evidence supports the more recently described hysterosalpingo-contrast sonography procedure as an acceptable screening study for the subfertile patient with the potential advantage that it is a comprehensive evaluation, methodologically simple, cost effective, and time efficient.
Fertility and sterility 03/2011; 95(7):2171-9. · 3.97 Impact Factor
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ABSTRACT: This study addressed the ability of genistein to reverse the loss of T-cell signaling components, induced by estrogen deficiency associated with aging.
Using Jurkat 6.1 T cells, genistein regulation of CD3zeta, JAK3, and NFkappaB was analysed by Western immunoblotting at 4 or 40 pg/mL (post- and pre-menopausal levels, respectively) estradiol (E(2)). Corresponding gene expressions were quantified by real-time polymerase chain reaction (RT-PCR). For functionality, levels of IL-2 were correlated with its transcription by RT-PCR.
At 4 pg/mL E(2), signaling proteins were decreased compared with 40 pg/mL: CD3zeta, 1.58-fold; JAK3, 1.75-fold; and NFkappaB, 1.73-fold (P < 0.001). Genistein, at 0.5 and 5.0 microm, added to 4 pg/mL E(2) induced their expression to 40 pg/mL levels. While significantly diminished IL-2 mRNA levels were observed at 4 pg/mL E(2), genistein induced IL-2 mRNA to 40 pg/mL levels.
Genistein restores CD3zeta, NFkappaB and JAK3 proteins and mRNAs at post-meonopausal estrogen levels, in vitro, with no significant effect at pre-menopausal estrogen levels.
American Journal Of Reproductive Immunology 01/2009; 61(1):26-33. · 2.17 Impact Factor
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ABSTRACT: Immunosenescence is an age-associated disorder occurring primarily in T cell compartments, including altered subset composition, functions, and activation. In women, evidence implicates diminished estrogen in the postmenopausal period as a contributing factor to diminished T cell responsiveness. Since hypoestrogenism is present in postmenopausal women, our objective focused on whether T cell activation, defined as signalling molecule expressions and activation, and function, identified as IL-2 production, were affected by low estrogen.
Using Jurkat 6.1 T cells, consequences of 4 pg/ml (corresponding to postmenopausal levels) or 40 pg/ml (premenopausal levels) of estradiol (E(2)) were analyzed on signalling proteins, CD3-zeta, JAK2, and JAK3, determined by Western immunoblotting. These consequences were correlated with corresponding gene expressions, quantified by real time-polymerase chain reaction. Tyrosine phosphorylation of CD3-zeta was defined by immunoprecipitation and western immunoblotting following activation by T cell receptor (TcR) cross-linking. CD3-zeta expression and modulation was also confirmed in T cells from pre- and postmenopausal women. To assess functional consequences, IL-2 production, induced by PMA and ionomycin, was determined using enzyme-linked immunosorbent spot assay (ELISpot).
At 40 pg/ml E(2), the level of signalling protein CD3-zeta was elevated 1.57-fold, compared with cells exposed to 4 pg/ml E(2). The CD3-zeta proteins also exhibited altered levels of activation-induced phosphorylation in the presence of 40 pg/ml E(2) versus 4 pg/ml: 23 kD phosphorylated form increased 2.64-fold and the 21 kD form was elevated 2.95-fold. Examination of kinases associated with activation signalling also demonstrated that, in the presence of 40 pg/ml E(2), JAK2 protein expression was increased 1.64-fold (p < 0.001) and JAK3 enhanced 1.79-fold (p < 0.001) compared to 4 pg/ml. mRNA levels for CD3-zeta, JAK2, and JAK3 were significantly increased following exposure to 40 pg/ml E(2) (2.39, 2.01, and 2.21 fold, respectively) versus 4 pg/ml. These findings were confirmed in vivo, since T cells from postmenopausal women exhibited 7.2-fold diminished CD3-zeta expression, compared to pre-menopausal controls and this expression was elevated 3.8-fold by addition of 40 pg/ml E(2). Functionally, Jurkat cells exposed to 40 pg/ml E(2) and activated exhibited significantly elevated numbers of IL-2 producing colonies compared to 4 pg/ml (75.3 +/- 2.2 versus 55.7 +/- 2.1 colonies, p < 0.0001).
Jurkat T cells exposed to 4 pg/ml E(2) expressed significantly diminished activation signalling proteins, correlating with reduced IL-2 production. Lower signalling protein levels appear to result from decreased CD3-zeta, JAK2, and JAK3 gene expressions. These findings may provide a molecular basis for immunosenescence associated with the postmenopausal state.
Immunity & Ageing 01/2009; 6:1.
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ABSTRACT: To investigate the effects of Müllerian-inhibiting substance (MIS) on cytochrome P450 aromatase (CYP19) gene expression in cultured human granulosa lutein cells (GLC).
In vitro primary cell culture study.
Academic research laboratory and hospital-based fertility center.
Eight normo-ovulatory patients undergoing IVF procedures due to male factor or tubal infertility.
Serum and follicular fluid (FF) collected and stored at -80 degrees C until assayed. Granulosa lutein cells were harvested from follicular aspirates obtained during oocyte retrieval and cultured for 7 days with media in the presence or absence of MIS (10 ng/mL) or FSH 0.2 IU/mL.
Serum and FF levels of E2 and MIS, and E2 production by GLC in culture. Levels of CYP19 mRNA in cultured GLC were determined by quantitative polymerase chain reaction (PCR) and CYP19 protein by Western blot. Statistical comparison used ANOVA and post hoc Tukey tests.
Follicle-stimulating hormone significantly increased E2 production in cultured GLC compared with control. The increase in E2 production is associated with higher levels of CYP19 mRNA and protein in GLC. The presence of MIS significantly inhibited FSH-induced E2 production, with concomitant reduction in CYP19mRNA and protein levels.
Müllerian-inhibiting substance inhibits FSH augmentation of CYP19 enzyme activity and CYP19 gene expression in GLC. These findings may help to explain the association of high MIS levels and low FF E2 levels reported in women with polycystic ovary syndrome (PCOS).
Fertility and sterility 06/2008; 89(5 Suppl):1364-70. · 3.97 Impact Factor
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ABSTRACT: To discuss an additional option for frozen embryos that can be a life-saving alternative.
Case report and literature review.
Academic fertility center.
A woman with a previous hysterectomy and frozen embryos who had a daughter afflicted with aplastic anemia.
Four thawed multicell embryos were transfered to the patient's 37-year-old multiparous sister.
Alternative disposition of frozen embryos.
The HLA type of the infant was found to be an exact match for the daughter dying from aplastic anemia.
The use of frozen embryos to prolong an existing individual's life is an additional ethical option to be considered by couples and individuals with cryopreserved embryos.
Fertility and sterility 12/2007; 90(3):849.e15-6. · 3.97 Impact Factor
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ABSTRACT: To characterize the hourly profiles of hCG secretion in blood during conceptive cycles that ended in successful pregnancy.
Prospective study.
University fertility clinic and research laboratories.
Healthy spontaneously ovulating women with regular menses, no history of infertility, and either no male partner or an azospermic partner.
Frequent blood samples were collected daily from 11 spontaneously ovulating women during 11 cycles of artifical insemination with donor semen. The concentrations of hCG, LH, and FSH were measured in the blood by immunoassay.
The concentration of hCG in the frequent blood samples and the rate that the concentration of hCG changed during the period of frequent sampling.
For the conceptive cycles resulting in successful pregnancies analyzed, hourly hCG concentrations were observed to increase in a consistent nonpulsatile manner.
These data provide the first characterization of the hourly secretion profile of hCG in early pregnancy as well as provide further evidence that individual daily blood samples are sufficient for the accurate assessment of pregnancy.
Fertility and sterility 07/2007; 87(6):1413-8. · 3.97 Impact Factor
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ABSTRACT: A combination of E and progestogens significantly increased matrix metalloproteinase (MMP)-2 in both T47D cells (E(2)-medroxyprogesteroneacetate [MPA] and E(2)-P) and MCF-7 cells (E(2)-MPA, E(2)-P, and equilin-MPA). All combinations resulted in higher MMP-9 levels in MCF-7 cells, but higher MMP-9 levels resulted only with equilin-norethinderone in T47D cells.
Fertility and sterility 05/2007; 87(4):978-81. · 3.97 Impact Factor
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ABSTRACT: New low-dose formulations of combination oral contraceptives (COCs) are safe and effective, but they may be associated with an increased risk of breakthrough bleeding. Extending the duration of active hormonal treatment may reduce the frequency of intracyclic bleeding/spotting while maintaining efficacy and tolerability.
This 6-month, open-label, randomized, active-controlled study involved healthy women aged 18-45 years who were at risk for pregnancy. Women were randomized 4:1 to a 24-day regimen of norethindrone acetate 1 mg/ethinyl estradiol 20 micro g (NETA/EE-24) or to a 21-day regimen of the same combination (NETA/EE-21). The outcomes assessed included pregnancy and incidence, duration of bleeding and intensity of bleeding.
The cumulative risk of pregnancy in the NETA/EE-24 group (n=705) was 0.9% during six cycles of treatment. Compared with NETA/EE-21 (n=181), NETA/EE-24 was associated with significantly fewer intracyclic bleeding days (0.95 vs. 1.63; p=.005), fewer days of withdrawal bleeding (2.66 vs. 3.88; p<.001) and fewer total bleeding/spotting days for Cycles 2-6 (18.6 vs. 23.2; p<.001). NETA/EE-24 was well tolerated, and side effects were generally mild to moderate in severity.
NETA/EE-24 is an effective well-tolerated COC that is associated with a bleeding profile more favorable than that of NETA/EE-21.
Contraception 02/2007; 75(1):16-22. · 2.72 Impact Factor
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ABSTRACT: It is known that women who smoke cigarettes and use oral contraceptives are more likely to have breakthrough bleeding than women who do not smoke. In this article, we review possible mechanisms by which cigarette smoke and its constituents may contribute to irregular bleeding, highlight differences in the activities of nicotine and cigarette smoke, and postulate further studies in the area.
Contraception 07/2006; 73(6):562-5. · 2.72 Impact Factor
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ABSTRACT: Matrix metalloproteinases (MMPs) may have a role in the pathogenesis of endometrioma. The level of MMP was lower compared to the level taken after resection of endometrioma.
Fertility and sterility 07/2006; 85(6):1847-8. · 3.97 Impact Factor
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ABSTRACT: Randomized trials in postmenopausal women have shown a benefit to substituting aromatase inhibitors for tamoxifen or using them sequentially following a full course of tamoxifen. The aromatase inhibitor letrozole has also been utilized for ovarian induction in premenopausal women.
A premenopausal woman with early stage breast cancer became amenorrheic with adjuvant chemotherapy, and remained so during 5 years of daily tamoxifen. After discontinuing tamoxifen, laboratory studies confirmed an apparent postmenopausal state. Menses resumed following a 2-week course of letrozole.
Aromatase inhibitors need to be used with caution in women who stop menstruating following adjuvant chemotherapy or tamoxifen.
Cancer Investigation 04/2006; 24(2):174-7. · 1.85 Impact Factor
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ABSTRACT: We studied the activity levels of matrix metalloproteinase 1, 2, and 9 in periovulatory fluids from naturally occurring menstrual cycles versus those from samples taken from menstrual cycles stimulated with clomiphene citrate or recombinant stimulating hormone. No statistically significant differences were found.
Fertility and sterility 04/2006; 85(3):800-1. · 3.97 Impact Factor
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ABSTRACT: The plasma profiles of active metalloproteinase (MMP)-1, MMP-2, and MMP-9 levels during the normal menstrual cycle in ovulating, healthy and tubal ligated patients were studied. The active MMP-1 and MMP-9 plasma levels were found to vary in the menstrual cycle. Active MMP-2 levels, however, are constant during the menstrual cycle.
Fertility and sterility 01/2006; 84(6):1766-7. · 3.97 Impact Factor
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ABSTRACT: To characterize the profiles of human chorionic gonadotropin (hCG) secretion in blood and its subsequent excretion in urine during conceptive cycles that ended in successful pregnancy and in spontaneous abortion.
A prospective study.
University fertility clinic and research laboratories.
Healthy, spontaneously ovulating women with regular menses, no history of infertility, and either no male partner or an azoospermic partner.
Blood and urine samples were collected daily from 63 spontaneously ovulating women during 167 cycles of artificial insemination (AI) with donor semen; hCG concentrations were measured in blood and urine, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations were measured in blood by immunoassay.
Fecundity, the day of ovulation, the day of hCG detection, and the concentration of hCG on the day of detection in blood and urine.
In 62 conceptions detected, 14 resulted in clinical spontaneous abortion (CAB) and 8 resulted in early pregnancy loss (EPL). When successful pregnancies and pregnancy losses were compared, no significant differences existed between the days of hCG appearance in serum or in urine, the concentrations of hCG on the day of detection, or the incremental change in hCG concentration on the day of detection.
These data validate the use of urinary hCG as a biomarker for assessing peri-implantation pregnancy events.
Fertility and sterility 05/2005; 83(4):1000-11. · 3.97 Impact Factor
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ABSTRACT: This study demonstrates significant differences in the midluteal concentrations of active matrix metalloproteinase (MMP)-1, MMP-2, and total MMP-3 between patients who conceived and those who did not after day 3 ET.
Fertility and Sterility 11/2004; 82(4):966-7. · 3.56 Impact Factor
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ABSTRACT: A multitude of female congenital anomalies are uncommon. However, their impact on reproduction can be profound. The aim of this review is to remind the practicing physician of the clinically relevant embryology and summarize the studies that look at the impact of such various anomalies on a woman's fecundity. We review particular surgical therapies that possibly may improve fertility in such women.
Review and critique of available studies in which particular surgical therapies were done and whether they truly improved fertility in these women with congenital reproductive anomalies.
Clear evidence demonstrates that uterine septum resection is effective in women with demonstrated recurrent pregnancy losses. Arcuate uterus has little impact on reproduction. Other studies fail to definitively show that surgical correction will improve pregnancy retention or fertility except for specifically indicated clinical scenarios.
The practicing reproductive specialist should have working knowledge of evidence-based therapeutic options for women with reproductive congenital anomalies. A summary chart has been devised to clearly associate embryologic structures with normal adult derivative as well as anomalous structures.
Fertility and Sterility 12/2002; 78(5):899-915. · 3.56 Impact Factor
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ABSTRACT: To evaluate urinary follicle-stimulating hormone (FSH) as a biomarker for the day of ovulation.
Prospective observational study.
Clinical research center.
Thirteen women were monitored with measurements of serum and urinary hormones and ovarian ultrasonography during 20 menstrual cycles. Data on urinary hormones and ultrasound evaluations from a total of 65 menstrual cycles from 42 women were analyzed.
Blood and/or urine samples were collected daily. Daily transvaginal ultrasonography was used to detect follicular collapse.
LH, FSH, and E(2) were measured in serum. FSH, estrone conjugates (E1C), and pregnanediol-3-glucuronide (PdG) were analyzed in urine. The day of luteal transition (DLT) was calculated using two algorithms.
In 20 cycles, the urinary FSH peak was closer to the day of follicular collapse (-0.85 days) than was the peak day of serum E(2) and the day of luteal transition, as calculated by one algorithm. The FSH peak was not closer to the day of follicular collapse than the peak values of urinary LH, serum FSH, or the day of luteal transition as calculated by a second algorithm. The most consistent correspondence between a hormone peak and ovulation was for serum E(2), serum FSH, serum LH, and urinary FSH. In 65 cycles for which urinary hormone data and ultrasound evaluations were available, the urinary FSH peak occurred within 1 day of follicular collapse in 97% of cycles.
Urinary FSH is a useful biomarker for estimating the day of ovulation in population-based studies.
Fertility and Sterility 06/2002; 77(5):961-6. · 3.56 Impact Factor
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ABSTRACT: Soy contains the isoflavone phytoestrogens, genistein and daidzein. These isoflavones are partial estrogen agonists in cell and animal models, but effects from dietary soy in humans are unclear. Experiments were conducted in pre- and postmenopausal women to examine whether dietary isoflavones from soy behave as estrogen agonists, antagonists or have no effect on the estrogen-sensitive pituitary. Pituitary sensitivity to gonadotropin-releasing hormone (GnRH), an estrogen-sensitive endpoint, was measured during GnRH challenge tests administered before, during and after dietary soy consumption. The response to an isoflavone-rich soy food diet was examined in five premenopausal and seven postmenopausal women using transdermal estrogen replacement therapy. Estrogen agonists suppress gonadotropin concentrations and enhance GnRH priming (enhanced gonadotropin secretion in response to repeated doses of GnRH), whereas antagonists elevate gonadotropin concentrations and have no effect on GnRH priming. Each subject consumed 50 g textured soy protein containing 60 mg total isoflavones daily for 10-14 d. Baseline estradiol concentrations were consistent among study periods. In both pre- and postmenopausal women, soy consumption did not affect mean baseline or peak luteinizing hormone (LH) concentrations, indicating a lack of estrogen-like effect at the level of the pituitary. However, in postmenopausal subjects, mean LH secretion decreased after discontinuing soy, suggesting a residual estrogenic effect. In one premenopausal woman, enhanced LH secretion was observed after soy treatment, suggesting there may be subpopulations of women who are highly sensitive to isoflavones.
Journal of Nutrition 05/2002; 132(4):708-14. · 3.92 Impact Factor
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Fertility and Sterility 04/2002; 77(3):635-7. · 3.56 Impact Factor
