Chelsi Goodman

PreImplantation Factor (PIF) correlates with early mammalian embryo development-bovine and murine models

BackgroundPreImplantation Factor (PIF), a novel peptide secreted by viable embryos is essential for pregnancy: PIF modulates local immunity, promotes decidual pro-adhesion molecules and enhances trophoblast invasion. To determine the role of PIF in post-fertilization embryo development, we measured the peptides concentration in the culture medium and tested endogenous PIFs potential trophic effects and direct interaction with the embryo.MethodsDetermine PIF levels in culture medium of multiple mouse and single bovine embryos cultured up to the blastocyst stage using PIF-ELISA. Examine the inhibitory effects of anti-PIF-monoclonal antibody (mAb) added to medium on cultured mouse embryos development. Test FITC-PIF uptake by cultured bovine blastocysts using fluorescent microscopy.ResultsPIF levels in mouse embryo culture medium significantly increased from the morula to the blastocyst stage (ANOVA, P = 0.01). In contrast, atretic embryos medium was similar to the medium only control. Detectable - though low - PIF levels were secreted already by 2-cell stage mouse embryos. In single bovine IVF-derived embryos, PIF levels in medium at day 3 of culture were higher than non-cleaving embryos (control) (P = 0.01) and at day 7 were higher than day 3 (P = 0.03). In non-cleaving embryos culture medium was similar to medium alone (control). Anti-PIF-mAb added to mouse embryo cultures lowered blastocyst formation rate 3-fold in a dose-dependent manner (2-way contingency table, multiple groups, X2; P = 0.01) as compared with non-specific mouse mAb, and medium alone, control. FITC-PIF was taken-up by cultured bovine blastocysts, but not by scrambled FITC-PIF (control).ConclusionsPIF is an early embryo viability marker that has a direct supportive role on embryo development in culture. PIF-ELISA use to assess IVF embryo quality prior to transfer is warranted. Overall, our data supports PIFs endogenous self sustaining role in embryo development and the utility of PIF- ELISA to detect viable embryos in a non-invasive manner.

The association of Apoprotein E polymorphisms with recurrent pregnancy loss.

Problem  We have previously reported the role of polymorphisms of thrombogenic genes involved in coagulation and fibrinolysis as risk factors for recurrent pregnancy loss. Thrombophilia has been viewed as a multigenic disorder rather than a monogenetic clinical phenotype and Apo E has been shown to play an important role in lipid metabolism in pregnancy. As individuals carrying the E4 allele of the ApoE gene have the highest risk for thrombosis, we evaluated the frequency of the Apo E4 genotype among women suffering from recurrent pregnancy loss.

Are polymorphisms in the ACE and PAI-1 genes associated with recurrent spontaneous miscarriages?

Problem  To determine whether the ACE D/D genotype or the combination of PAI‐1 4G/4G and ACE D/D genotypes may serve as a risk factor for recurrent pregnancy loss.

ORIGINAL ARTICLE: The Association of Apoprotien E Polymorphisms with Recurrent Pregnancy Loss

Problem  We have previously reported the role of polymorphisms of thrombogenic genes involved in coagulation and fibrinolysis as risk factors for recurrent pregnancy loss. Thrombophilia has been viewed as a multigenic disorder rather than a monogenetic clinical phenotype and Apo E has been shown to play an important role in lipid metabolism in pregnancy. As individuals carrying the E4 allele of the ApoE gene have the highest risk for thrombosis, we evaluated the frequency of the Apo E4 genotype among women suffering from recurrent pregnancy loss.

ORIGINAL ARTICLE: Are Polymorphisms in the ACE and PAI-1 Genes Associated with Recurrent Spontaneous Miscarriages?

Problem  To determine whether the ACE D/D genotype or the combination of PAI‐1 4G/4G and ACE D/D genotypes may serve as a risk factor for recurrent pregnancy loss.

ORIGINAL ARTICLE: The Association of Apoprotien E Polymorphisms with Recurrent Pregnancy Loss: APO E AND RPL

Problem  We have previously reported the role of polymorphisms of thrombogenic genes involved in coagulation and fibrinolysis as risk factors for recurrent pregnancy loss. Thrombophilia has been viewed as a multigenic disorder rather than a monogenetic clinical phenotype and Apo E has been shown to play an important role in lipid metabolism in pregnancy. As individuals carrying the E4 allele of the ApoE gene have the highest risk for thrombosis, we evaluated the frequency of the Apo E4 genotype among women suffering from recurrent pregnancy loss.

ORIGINAL ARTICLE: Are Polymorphisms in the ACE and PAI-1 Genes Associated with Recurrent Spontaneous Miscarriages?: POLYMORPHISMS IN THE ACE AND PAI-1 GENES

Problem  To determine whether the ACE D/D genotype or the combination of PAI‐1 4G/4G and ACE D/D genotypes may serve as a risk factor for recurrent pregnancy loss.

Age Related Serum Antimullerian Hormone Concentrations among Infertile Versus Fertile Women

Aims: Antimullerian hormone (AMH) has been accepted as a marker for the size of the ovarian follicle pool. To interrupt the results of this investigation, age-specific concentrations are needed. The purpose of this study is to compare antimullerian hormone (AMH) concentrations among infertile women ages 22 to 32 years experiencing regular menses with oocytes donors of the same age. Study Design: Cohort study. Place and Duration of Study: South Florida Institute for Reproductive Medicine, Miami, Florida and Reproductive Medicine Institute, Evanston, IL. Samples drawn between June 2008 Original Research Article Goodman et al.; JAMPS, 2(2): 70-74, 2015; Article no.JAMPS.2015.010 71 and June 2012. Methodology: 400 infertile women and 102 oocyte donors aged 22-32 years with a history of regular menses and who were undergoing in vitro fertilization procedures for treatment of infertility had blood drawn for determination of AMH concentrations. Serum AMH was measured by enzymelinked immunosorbent assay using an AMH ELISA kit (Beckman Coulter, Chaska, MN, USA). Results: When the mean +2 standard deviations of the serum AMH concentrations among infertile women with regular menses were compared with age-specific oocyte donors, a significant decrease among infertile women was noted at all age groups. Conclusion: A significant proportion of infertile women have lower than average ovarian reserve, suggesting that serum AMH values reflect follicular supply somewhat independent of age.

Are Antimullerian Hormone and its Receptor Genes Associated with Low Ovarian Response

Are Antimullerian Hormone and its Receptor Genes Associated with Low Ovarian Response? One of the most frustrating problems in the treatment of infertility is that of poor ovarian response to stimulation. It therefore, would be advantageous to have a genetic marker that could predict low ovarian reserve at a young age before the impact of low ovarian reserve affects a woman’s fertility. Antimullerian hormone (AMH) has emerged as the the most accurate measure of ovarian reserve. The purpose of the present study is to investigate the correlation between AMH and AMH Receptor II (AMHRII) polymorphisms and low ovarian reserve.

LETTER TO THE EDITOR: The Association of Apoprotein E Polymorphisms with Recurrent Pregnancy Loss

To the editor: We agree with Drs Zhang and Wu that apolipoprotein (Apo) E genotype distribution may differ among populations and that larger studies are necessary to confirm the association of Apo E3 ⁄ E4+ E4 ⁄ E4 genotypes and recurrent pregnancy loss (RPL). That said, we have shown significant associations of Apo E3 ⁄ E4+ E4 ⁄ E4 genotypes in both United States and Turkish populations. We should, however, like to clarify two points made by Drs Zhang and Wu. The first point relates to the allelic frequency of Apo E4. Drs Zhang and Wu note that the Apo E4 allelic frequency has been reported to be around 26% in healthy subjects which they state is higher than that of RPL patients reported by Goodman et al. In fact, the allelic frequency of Apo E4 was not reported in the Goodman paper, but was reported in the Ergin et al. study. Ergin et al. reported an Apo E4 allelic frequency of 22.8%, which was not significantly different from that in their fertile controls (P = 0.16). However, when the frequency of Apo E3 ⁄ E4 and E4 ⁄ E4 genotypes were compared (eliminating E2 ⁄ E4 genotypes from the comparison as this genotype is not a risk factor for cardiovascular disease), significantly more Apo E3 ⁄ E4 and E4 ⁄ E4 genotypes were seen among individuals experiencing RPL than fertile controls (P < 0.05). The low frequency of Apo E3 ⁄ E4+ E4 ⁄ E4 genotypes might not influence the rate of Type I errors as much as the specificity of the marker. By definition, significance was assumed at P < 0.05%. By adoption of a = 95%, the false positive or Type I error rate is kept at <5%. The second point to be clarified is the importance of study design and positive controls. The Bianca et al. paper cited by Drs Zhang and Wu compared the prevalence of Apo E3 ⁄ E4+ E4 ⁄ E4 genotypes among women experiencing RPL with women with a history of cardiovascular disease (CVD) and women with a family history of inherited thrombophilia. Their results showed the prevalence of Apo E3 ⁄ E4+ E4 ⁄ E4 genotypes to be 14.3% among women with a history of RPL, 16% for women with a history of CVD and 24% for women with a family history of inherited thrombophilia. On the basis of no differences between their study group and their positive controls, the authors concluded that there was ‘‘no association between apolipoprotein E polymorphisms and recurrent pregnancy loss’’. However, to come to this conclusion, appropriate negative controls are necessary. Bianca et al. reported no negative controls. Appropriate negative controls were reported in the Goodman et al. and Ergin et al. studies. The prevalence of Apo E3 ⁄ E4+ E4 ⁄ E4 genotypes among women with at least two live births and no history of thrombophilia was 5%. When we compared the frequency of Apo E3 ⁄ E4+ E4 ⁄ E4 genotypes between women experiencing RPL (21.7%) and individuals with a history of deep vein thrombosis (DVT) (17%), no significant difference was observed. The frequency of Apo E3 ⁄ E4+ E4 ⁄ E4 genotypes was 5% in our negative fertile controls and 17% in our positive DVT controls (data for DVT not previously reported). Thus, as we have previously stated, Apo E4 polymorphisms may contribute to the thrombogenic risk factors contributing to RPL. However, inherited thrombophilia represents multiple gene defects rather than any single gene defect.