scholarly journals Longer Duration and Proper Titration of Low Molecular Weight Heparin (LMWH), Are Independent Factors for Successful Pregnancy Outcome. Retrospective Analysis from a Single Center

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5065-5065
Author(s):  
Maria Stamou ◽  
Stergios Intzes ◽  
Eleftheria Lamprianidou ◽  
Menelaos Konstantinos Papoutselis ◽  
Zoe Bezirgiannidou ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Live Birth ◽  
Pregnancy Complications ◽  
Pregnancy Loss ◽  
Single Center ◽  
Successful Pregnancy ◽  
Live Births ◽  
Continuous Parameter ◽  
At Iii ◽  
Thrombophilia Screening

Abstract The role of thrombophilia and LMWH use in pregnancy loss (PL) and pregnancy complications (PC) is debated. In this retrospective study from a single center we analyzed the clinical outcome of pregnancies in relation to thrombophilic factors and the use of LMWH, aspirin and folic acid in 143 women followed up for a total of 173 pregnancies referred to our center from 2003 to 2016. Methods: Women were referred to our unit for: more than 2 unexplained PL (n=96, 78 experienced only early PL, 11 had only late PL, 7 had both early and late), one pregnancy loss(n=45) or one pregnancy complication (placenta abruption, intrauterine growth restriction, eclampsia, n=2). Mutations in Factor V-Leiden (FVL, G1691A), Prothrombin (PTG, G20210A) and MTHFR (C677T, A 1206C) were checked by DNA hybridization Kit. Plasma levels of antithrombin-III, protein-C, free Protein-S, APCR, FVIII, FXII, PT aPTT, fibrinogen, homocysteine and La-test were measured by photometry (DACO). Anticardiolopin and anti-β2GPI antibodies (IGG and IGM) were measured by ELISA in serum (APLA). End points were live birth and pregnancy complications. The prevalence of thrombophilia in our cohort was similar with previous studies and 34/143 (23,4%) women were negative for all thrombophilic factors. We observed mutations in FVL(11,6%), PTG (9,6%), MTHFR (homozygous or double heterozygous, 33,3%) and deficiencies of AT-III (3,3%), Prot-C (1,6%), Prot-S (8,8%), APS (8,7%). Combined severe trombophilic factors were found in 31 women (21,5%) (FVL+PTG 4/31, Natural Anticoagulants one out 3 Def + MTHFR 3/31, APS + MTHFR 2/31, FVL+MTHFR 16/31, PTG + MTHFR 6/31). We then separated our cohort into women with <2 complications or women with >2 complications. The second group had significantly higher incidence of FVL mutation (12,5 vs 8,3%, p=0.05) and deficiencies of AT-III and Free Prot-S ( 6,5 vs 0 %, p=0.01) compared to the first one. By contrast, women in the first group had higher incidence of La-test (12,5 vs 4,5%, p=0,03), APLA ( 12 vs 6,6%, p=0.03) and Prot.C deficiency (4,5 vs 0%, p=0.01). In univariate analysis both hereditary and acquired thrombophilic factors did not correlated with pregnancy outcome (live birth or pregnancy complications). Only age as a continuous parameter correlated negatively with live birth and positively with pregnancy complications (p=0.01 and p=0.025, respectively), whereas high BMI as a continuous parameter also negatively affected live births (p= 0.049). Logistic regression analysis reveals that the age of 35 is the cut off for unfortunate pregnancy outcome. Pregnancies were proceeded with (n=143, 81,7%) or without (n=32, 18,3%,) LMWH. The decision to use LMWH were based in a positive thrombophilia screening test (n=84) or to prior history >2 pregnancy complications with negative trombophilia testing (n=59). Concomitant use of ASA was prescribed in 78 pregnancies (dose less than 100 mg/day) and concomitant follic acid in 143 pregnancies. The percentage of live births were identical in women treated with LMWH (87,4%) or not (87,5%, p=0.9). In multivariate analysis, the only factor that was strongly correlated to live birth was the duration of LMWH treatment (odds ratio, OR =3,567, 95% CI (1.845, 6,894), p= 0,01) and the titration of the dose with anti-Xa (OR=5,138, 95% CI (1,717, 15,376), p = 0,01, fig.1a). By ROC analysis the duration of LMWH which correlated to live birth was ≥ 5.5 months(fig. 1b). The addition of ASA was insignificant for live birth (p=0.7), while the duration (>6months) of follic acid also appeared to add a benefit in combination with LMWH (p=0.01). Moreover, pregnancies proceeded without LMWH exhibited higher rates of pregnancy complications (18,75 vs 11,2%, p=0.08) and prematurity (14,3 vs 8,8%, p=0.05). In summary, our findings argue against hereditary thrombophilia screening in the cases of previous pregnancy loss or pregnancy complications. On the contrary, testing for APS even after the first event might be of value as this population often has laboratory evidence of APS and may benefit from proper anticoagulation. The use of LMWH and folic acid but not of ASA was related to less pregnancy complications or prematurity, whereas proper titration of LMWH by using anti-Xa and long duration of therapy were the only important factors for successful pregnancy outcome. Disclosures No relevant conflicts of interest to declare.

scholarly journals POS0737 LOW PRECONCEPTIONAL COMPLEMENT LEVEL IS RELATED WITH ADVERSE OBSTETRIC OUTCOME IN A MULTICENTRIC COHORT OF PREGNANCY IN PATIENTS WITH APS AND APL POSITIVITY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 619.2-620
Author(s):  
D. Lini ◽  
C. Nalli ◽  
L. Andreoli ◽  
F. Crisafulli ◽  
M. Fredi ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Complement Activation ◽  
Pregnancy Complications ◽  
Antiphospholipid Antibodies ◽  
Pregnancy Loss ◽  
Adverse Pregnancy Outcome ◽  
Obstetric Outcome ◽  
Complement Level ◽  
Increased Risk ◽  
Adverse Pregnancy

Background:The role of complement in the antiphospholipid (aPL) related pathology has been widely studied in animal models. Antiphospholipid antibodies can induce fetal loss in experimental animals but mice deficient in specific complement components (C4, C3, C5) appear somehow protected. In addition, in pregnant mice injected with aPL, antibody deposition has been found at decidual level causing focal necrosis, apoptosis and neutrophil infiltrates and supporting aPL pathogenetic potential. On the other hand, human studies did find hypocomplementemia associated to pregnancy complications in patients with obstetric antiphospholipid syndrome (APS). These results, however, are not unanimously confirmed and, in addition, some studies only show increased levels of complement activation products (i.e. Bb) and not decreased levels of C3 and/or C4. A recently study focusing on complement level in early pregnancy and before pregnancy showed a significant correlation with pregnancy complications and loss in a large cohort of primary APS.Objectives:To investigate if the simple detection of low C3 and/or C4 could be considered a risk factor for adverse pregnancy outcome in APS and aPL carriers pregnancies.Methods:We performed a multicentric study including patients from 10 Italian and 1 Russian Centers. Data on pregnancies in women with primary APS (n=434) and asymptomatic carriers with persistently positive aPL but not fulfilling clinical criteria for APS (n=218) were retrospectively collected. Serum C3 and C4 levels were evaluated by nephelometry; hypocomplementemia was defined by local laboratory reference values. Statistical analysis was performed using GraphPad.Results:Preconceptional complement levels and gestational outcome were available for 107 (25%) pregnancies in APS out of 434 and for 196 (90%) pregnancies in aPL carriers women out of 218. In pregnancies with low preconceptional C3 and/or C4, a significantly higher prevalence of pregnancy losses was observed (p=0.019). A subgroup analysis focusing on triple aPL positive patients was also performed. Preconceptional low C3 and/or C4 levels were found to be associated with an increased rate of pregnancy loss (p = 0.027) in this subgroup also. Otherwise, adverse pregnancy outcomes in single or double aPL positive women were not related to preconception complement levels (p = 0.44) (Table 1). Of note, all the pregnancy losses in the triple positive group occurred in patients treated with low dose aspirin and low molecular weight heparin from the time of positive pregnancy test.Conclusion:Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of adverse outcome. This has been seen only in in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss. test positivity.References:[1]De Carolis S, et al. Complementemia and obstetric outcome in pregnancy with antiphospholipid syndrome. Lupus (2012) 21:776–8.[2]Kim MY, et al. Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies. Ann Rheum Dis (2018) 77:549–55.[3]Fredi M, et al. Risk Factors for Adverse Maternal and Fetal Outcomes in Women With Confirmed aPL Positivity: Results From a Multicenter Study of 283 Pregnancies. Front Immunol. 2018 May 7;9:864.Triple aPL positivitySingle or double aPL positivityGestational outcomeLow C3/C4 (n=49)Normal C3/C4(n=17)pLow C3/C4 (n=57)Normal C3/C4(n=165)pTerm live birth (>37w)15 (31%)6 (35%)ns34 (60%)110 (67%)nsPreterm live birth (≤37w)22 (45%)11 (65%)ns15 (26%)38 (23%)nsPregnancy losses (abortion and miscarriages)12 (24%)0 (0%)0.0278 (14%) 17 (10%)nsDisclosure of Interests:None declared

scholarly journals HYdroxychloroquine to Improve Pregnancy Outcome in Women with AnTIphospholipid Antibodies (HYPATIA) Protocol: A Multinational Randomized Controlled Trial of Hydroxychloroquine versus Placebo in Addition to Standard Treatment in Pregnant Women with Antiphospholipid Syndrome or Antibodies

2017 ◽  
Vol 43 (06) ◽  
pp. 562-571 ◽  
Author(s):  
Karen Schreiber ◽  
Karen Breen ◽  
Hannah Cohen ◽  
Soren Jacobsen ◽  
Saskia Middeldorp ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Pregnancy Outcome ◽  
Pregnancy Outcomes ◽  
Pregnancy Complications ◽  
Antiphospholipid Antibodies ◽  
Pregnancy Loss ◽  
Standard Treatment ◽  
Randomized Controlled ◽  
Improve Pregnancy Outcome ◽  
Adverse Pregnancy

AbstractWomen with antiphospholipid antibodies (aPL) are at risk of adverse pregnancy outcomes, including recurrent first-trimester pregnancy loss and late pregnancy complications such as preeclampsia, HELLP (hemolysis, elevated liver enzyme levels, and low platelet levels) syndrome, premature delivery, intrauterine growth restriction, placental abruption, and intrauterine death. Current standard care in obstetric antiphospholipid syndrome includes aspirin and heparin and has resulted in live-birth rates of approximately 70%. However, 30% continue to have pregnancy complications. Hydroxychloroquine (HCQ) is suggested as a new treatment approach, but no randomized controlled trials (RCTs) have assessed its efficacy. This study aims to assess pregnancy outcome in women with aPL treated with HCQ versus placebo in addition to standard treatment. The HYdroxychloroquine to improve Pregnancy outcome in women with AnTIphospholipid Antibodies (HYPATIA) study is a phase IV multicenter RCT, in which pregnant women with persistent aPL will receive either HCQ or placebo in addition to their usual medication. The primary endpoint is a composite of aPL-related adverse pregnancy outcomes: one or more pregnancy loss(es) (either < 10 or > 10 weeks of gestation) and premature birth before 34 weeks due to any of the following preeclampsia, eclampsia, or recognized features of placental insufficiency. The HYPATIA study is expected to provide evidence on the effect of HCQ in pregnant women with persistent aPL.

Modulation of systemic hemostatic parameters by enoxaparin during gestation in women with thrombophilia and pregnancy loss

2005 ◽  
Vol 94 (11) ◽  
pp. 980-985 ◽  
Author(s):  
Zeev Blumenfeld ◽  
Ronit Leiba ◽  
Naomi Lanir ◽  
Benjamin Brenner ◽  
Galit Sarig
Keyword(s):  
Pregnancy Outcome ◽  
Pregnancy Loss ◽  
Protein S ◽  
Study Groups ◽  
Control Group ◽  
Activity Levels ◽  
Successful Pregnancy ◽  
Free Protein ◽  
Outcome Group ◽  
D Dimer

SummaryRecurrent pregnancy loss (PL) is associated with maternal thrombophilia and prophylaxis with low molecular weight heparin (LMWH) can improve pregnancy outcome in this setting. The aim of this study was to investigate the modulation of systemic hemostatic parameters by enoxaparin in women with recurrent PL and to evaluate plasmatic parameters that would potentially enable monitoring LMWH prophylaxis effect during pregnancy. Study group included 87 women with thrombophilia and PL treated with enoxaparin 40 mg daily vs. 40 mg twice daily. The control group comprised 40 women with normal pregnancies. Blood samples have been collected throughout the period starting at 5-10 weeks of gestation until 6-10 weeks postpartum. The determined plasmatic markers included: anti-Xa activity, total and free tissue factor pathway inhibitor (TFPI), D-dimer, prothrombin fragment 1+2 (PT1+2), activated protein C resistance (APC-SR) and free protein S. Successful pregnancy outcome was recorded in 70 (80.5%) women treated with enoxaparin, with-out correlation to enoxaparin dosage. Seventeen women (19.5%) had pregnancy loss at 16±7 (6-32) weeks of gestation. Anti-Xa levels at 10-15 weeks of gestation were higher (0.39±0.38 u/ml) in the successful pregnancy outcome group compared to the abortion group (0.22±0.2 u/ml). Prophylactic anti-Xa activity levels (0.28±0.13 u/ml) were documented from 15 weeks of gestation until delivery in the successful pregnancy outcome group. Significant increase in anti-Xa, total TFPI and free TFPI levels (P<0.001) was achieved after beginning of LMWH prophylaxis in successful pregnancy outcome group but not in the abortion group. D-dimer and PT1+2 levels appeared to be significantly increased while APC-SR and free protein S levels gradually decreased during pregnancy, with no difference between study groups. These results suggest that LMWH prophylaxis during pregnancy enables modulation of systemic hemostatic parameters via inhibition of factor Xa and increase in plasmatic total and free TFPI levels.

scholarly journals Investigation of Cumulus Cell Factors Associated With Embryo Development and Pregnancy Outcome in Human IVF

2021 ◽  
Author(s):  
◽  
Jozsef Ekart
Keyword(s):  
Candidate Genes ◽  
Pregnancy Outcome ◽  
Live Birth ◽  
Young Women ◽  
Pregnancy Outcomes ◽  
Mrna Levels ◽  
Successful Pregnancy ◽  
Expression Levels ◽  
Healthy Women ◽  
Qpcr Method

<p>Recent evidence suggests that the expression of some candidate genes in cumulus cells (CC) have the potential to serve as markers of oocyte quality. The aims of this study were: 1) to validate a multiplex quantitative polymerase chain reaction (QPCR) method to measure four genes simultaneously in extracts from individual CC and; 2) to investigate the relationships in individual cumulus-oocyte-complexes (COC) amongst the expression levels of a range of candidate genes (N=8) from individual CC, the numbers of CC per COC and developmental indicators (good blastocyst development and live birth outcome) of the associated oocytes following in vitro fertilization (IVF) with intra-cytoplasmic sperm injection (ICSI). Sixty eight women were recruited for this study following approval from NZ Multi-Regional Ethics Committee and classified into four research groups: young and healthy women (<38 years, N=25), young women with polycystic ovarian syndrome (<38 years, N=11), young with diminished ovarian reserve (<38 years, N=12) and older and healthy women (≥40 years, N=20). Following exogenous rFSH-assisted ovarian stimulation, 608 COC were collected and subjected to ICSI. Oocyte and embryo quality, and pregnancy outcomes were recorded. Expression levels of the following candidate genes HAS2, FSHR, SLC2A4 (GLUT4), ALCAM, SFRP2, VCAN, NRP1 and PR in CC extracts from individual COC were measured by TaqMan QPCR and normalized against the house-keeping gene, RPL19. The numbers of CC from individual COC were calculated from RPL19 expression levels plotted against a standard curve of CC number. These results were then assessed against the outcomes of the associated oocytes following ICSI. HAS2, FSHR, ALCAM, VCAN, NRP1 and PR mRNA were detectable in most samples (98.5%) whereas those for SLC2A4 and SFRP2 were generally undetectable. The minimum number of CC required for QPCR was estimated to be ~70. The mean levels of FSHR mRNA were up-regulated in young women with PCOS compared to those in the other two groups of women <38y. Expression levels of HAS2 across all four groups of women were correlated to both biological (age, basal serum FSH and serum AMH) and treatment (amount of rFSH used for stimulation, follicle numbers and COC retrieved) variables. Investigations related to oocyte development in young and healthy women showed that 1) mean mRNA levels of VCAN, HAS2 and PR were higher (P=0.002, P<0.05, P<0.05, respectively) in CC associated with oocytes that resulted in good quality blastocysts and those of VCAN were higher (P<0.05) in CC associated with oocytes that resulted in a live birth, compared with those with developmental failure. However, the expression levels of all measurable candidate genes were highly variable for individual CC from COC from each woman. Indeed, 99.7% of individual COC were different in CC mRNA levels and cell composition. The application of a ranking method to score the relative CC mRNA levels of selected candidate genes from each COC recovered from individual women was evaluated. This approach demonstrated a predictive power of 80% efficiency for selecting good quality oocytes (at least one), whilst requiring the insemination of no more than three oocytes in any treatment cycle. Furthermore, this selection method resulted in a pregnancy and live birth rate of 60 and 52% respectively (N=25 women). This outcome is similar to that achieved when all metaphase II (MII) oocytes are inseminated. In conclusion, this study has validated a multiplex QPCR method to quantify the expression levels of four genes in CC of individual human COC simultaneously using as few as 70 cells. Moreover, that there is sufficient cDNA so that many more candidate genes can be measured in the same extract. From the knowledge of the mRNA levels of at least four genes, VCAN, FSHR, HAS2 and PR in CC, it is possible to improve upon existing biological indicators the potential to predict good blastocyst formation and a successful pregnancy outcome. It is concluded that the application of a multiplex QPCR approach to assess the expression levels of a limited number of marker genes in CC can be used to select the best oocytes for successful pregnancy outcomes.</p>

Thrombophilia and its impact on pregnancy

2008 ◽  
Vol 28 (03) ◽  
pp. 130-134 ◽  
Author(s):  
I. Pabinger
Keyword(s):  
Risk Factors ◽  
Molecular Weight ◽  
Pregnancy Outcome ◽  
Prospective Studies ◽  
Pregnancy Complications ◽  
Low Molecular Weight Heparin ◽  
Pregnancy Loss ◽  
Factor V Leiden ◽  
Low Molecular Weight ◽  
Increased Risk

SummaryIn recent years thrombophilia has gained much attention as a risk factor for pregnancy complications. Whereas there is an established correlation between antiphospholipid-antibodies and pregnancy loss, data for other risk factors of thrombosis are less well established. Data suggest associations with antithrombin deficiency, hyperhomocysteinemia and also with factor V Leiden, prothrombin G20210A variation and protein S-deficiency. The association of thrombophilia with pre-eclampsia is still under discussion. A limited number of prospective studies did not reveal an increased risk for pregnancy complications in unselected women with thrombosis risk factors. In a single study low molecular weight heparin seemed to have a positive effect on pregnancy outcome after previous single or recurrent abortions. Experience in prevention of pre-eclampsia by administration of prophylactic heparin is very limited. Data on pregnancy complications in women with known heritable thrombophilia or a history of thrombosis are inconsistent as well. These women usually have a favourable pregnancy outcome. Conclusion: Thrombophilia screening might be justified in women with pregnancy loss. Treatment with low molecular weight heparin might be considered for those with pregnancy loss and thrombophilia. Further prospective studies and controlled interventional trials are urgently needed.

scholarly journals Role of Human Chorionic Gonadotrophin Compared to 17-Alpha-Hydroxyprogesterone in the Management of Threatened Abortion: Experience in a Military Hospital in Dhaka, Bangladesh

2019 ◽  
Vol 9 (1) ◽  
pp. 7-10
Author(s):  
Shakila Khanum ◽  
Jamal Uddin Ahmed
Keyword(s):  
Pregnancy Outcome ◽  
Live Birth ◽  
Preterm Labor ◽  
Pregnancy Loss ◽  
Previous History ◽  
Military Hospital ◽  
Co Morbidity ◽  
Significant Difference ◽  
History Of ◽  
Threatened Abortion

Background: Threatened abortion is the most common complication in the first half of gestation. Spontaneous abortion occurs in less than 30% of the women who experience threatened abortion. In order to prevent pregnancy loss several supportive therapies including hormonal therapy like human chorionic gonadotropin (hCG) or 17-alpha-hydroxyprogesterone (progesterone) have been advocated. The exogenous administration of hCG is aimed at stimulating and therefore optimizing progesterone production. Aim of this study was to compare the efficacy of supportive therapy with hCG and progesterone in women with threatened abortion. Methods: This prospective study was carried out in the department of obstetrics and gynecology of the Combined Military hospital (CMH), Savar, Dhaka, Bangladesh from July 2016 to June 2017. One hundred pregnant patients admitted with the history of per vaginal bleeding before 20 weeks of gestation without having any other co-morbidity were included in this study. Patients were randomized to two treatment groups. The participants in group A (52, 52%) received injection hCG weekly while those in group B (48, 48%) received injection progesterone from recruitment up until 20 weeks of gestation. Further USG were performed one week and four weeks after recruitment to the study and again at 20 weeks and subsequently when indicated. The final outcome of pregnancy were recorded and analyzed. Results: Among 100 patients majority belonged to the 26-30 year age group. Mean age of the patients was 27.2±10.5 years. There was not much significant difference between the groups in terms of parity. More than 75% of patients in both the groups presented before 16 weeks of gestation with threatened abortion. In both the groups more than 75% of the patients had previous history of pregnancy loss. In terms of pregnancy outcome more patients in hCG group had live pregnancy than progesterone group (88.5% vs 66.7%) (p=0.012). Out of 46 live birth in hCG group, 4 (7.7%) were preterm labor between 31-35 weeks of pregnancy and one baby died in neonatal ICU, one died at 31 weeks of gestation which was delivered by vaginally. On the other hand out of 32 live birth in progesterone group, there was 3 (6.3%) preterm labor. Growth retardation was less in hCG group compared to progesterone group (9.6% vs 14.6%). However cesarean section rate was high in both the groups. Conclusion: Treatment with injection hCG has better pregnancy outcome than that of injection17-alphahydroxyprogesterone in early pregnancy with threatened abortion of unexplained cause. Birdem Med J 2019; 9(1): 7-10

scholarly journals Investigation of Cumulus Cell Factors Associated With Embryo Development and Pregnancy Outcome in Human IVF

2021 ◽  
Author(s):  
◽  
Jozsef Ekart
Keyword(s):  
Candidate Genes ◽  
Pregnancy Outcome ◽  
Live Birth ◽  
Young Women ◽  
Pregnancy Outcomes ◽  
Mrna Levels ◽  
Successful Pregnancy ◽  
Expression Levels ◽  
Healthy Women ◽  
Qpcr Method

<p>Recent evidence suggests that the expression of some candidate genes in cumulus cells (CC) have the potential to serve as markers of oocyte quality. The aims of this study were: 1) to validate a multiplex quantitative polymerase chain reaction (QPCR) method to measure four genes simultaneously in extracts from individual CC and; 2) to investigate the relationships in individual cumulus-oocyte-complexes (COC) amongst the expression levels of a range of candidate genes (N=8) from individual CC, the numbers of CC per COC and developmental indicators (good blastocyst development and live birth outcome) of the associated oocytes following in vitro fertilization (IVF) with intra-cytoplasmic sperm injection (ICSI). Sixty eight women were recruited for this study following approval from NZ Multi-Regional Ethics Committee and classified into four research groups: young and healthy women (<38 years, N=25), young women with polycystic ovarian syndrome (<38 years, N=11), young with diminished ovarian reserve (<38 years, N=12) and older and healthy women (≥40 years, N=20). Following exogenous rFSH-assisted ovarian stimulation, 608 COC were collected and subjected to ICSI. Oocyte and embryo quality, and pregnancy outcomes were recorded. Expression levels of the following candidate genes HAS2, FSHR, SLC2A4 (GLUT4), ALCAM, SFRP2, VCAN, NRP1 and PR in CC extracts from individual COC were measured by TaqMan QPCR and normalized against the house-keeping gene, RPL19. The numbers of CC from individual COC were calculated from RPL19 expression levels plotted against a standard curve of CC number. These results were then assessed against the outcomes of the associated oocytes following ICSI. HAS2, FSHR, ALCAM, VCAN, NRP1 and PR mRNA were detectable in most samples (98.5%) whereas those for SLC2A4 and SFRP2 were generally undetectable. The minimum number of CC required for QPCR was estimated to be ~70. The mean levels of FSHR mRNA were up-regulated in young women with PCOS compared to those in the other two groups of women <38y. Expression levels of HAS2 across all four groups of women were correlated to both biological (age, basal serum FSH and serum AMH) and treatment (amount of rFSH used for stimulation, follicle numbers and COC retrieved) variables. Investigations related to oocyte development in young and healthy women showed that 1) mean mRNA levels of VCAN, HAS2 and PR were higher (P=0.002, P<0.05, P<0.05, respectively) in CC associated with oocytes that resulted in good quality blastocysts and those of VCAN were higher (P<0.05) in CC associated with oocytes that resulted in a live birth, compared with those with developmental failure. However, the expression levels of all measurable candidate genes were highly variable for individual CC from COC from each woman. Indeed, 99.7% of individual COC were different in CC mRNA levels and cell composition. The application of a ranking method to score the relative CC mRNA levels of selected candidate genes from each COC recovered from individual women was evaluated. This approach demonstrated a predictive power of 80% efficiency for selecting good quality oocytes (at least one), whilst requiring the insemination of no more than three oocytes in any treatment cycle. Furthermore, this selection method resulted in a pregnancy and live birth rate of 60 and 52% respectively (N=25 women). This outcome is similar to that achieved when all metaphase II (MII) oocytes are inseminated. In conclusion, this study has validated a multiplex QPCR method to quantify the expression levels of four genes in CC of individual human COC simultaneously using as few as 70 cells. Moreover, that there is sufficient cDNA so that many more candidate genes can be measured in the same extract. From the knowledge of the mRNA levels of at least four genes, VCAN, FSHR, HAS2 and PR in CC, it is possible to improve upon existing biological indicators the potential to predict good blastocyst formation and a successful pregnancy outcome. It is concluded that the application of a multiplex QPCR approach to assess the expression levels of a limited number of marker genes in CC can be used to select the best oocytes for successful pregnancy outcomes.</p>

scholarly journals Quantitative assessment of pregnancy outcome following recurrent miscarriage clinic care: a prospective cohort study

2021 ◽  
Author(s):  
Rebecca C Shields ◽  
Omar Khan ◽  
Sarah N Lim Choi Keung ◽  
Amelia Hawkes ◽  
Aisling Barry ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Data Collection ◽  
Pregnancy Outcome ◽  
Live Birth ◽  
Pregnancy Loss ◽  
Recurrent Miscarriage ◽  
Modifiable Risk Factors ◽  
List Type

AbstractObjectivesTo measure pregnancy outcome following attendance at a recurrent miscarriage service and identify factors that influence outcome.DesignProspective, observational electronic cohort study.SettingParticipants attending specialist recurrent miscarriage clinic, within a tertiary centre, with a history of two or more pregnancy losses. The clinic serves a diverse population (33% of residents belong in a minority ethnic group and over 33% in low-income households). Participant data were recorded on a bespoke study database, ‘Tommy’s Net’.Participants777 women consented to participate. 639 (82%) women continued within the cohort, and 138 were lost to follow up. Mean age of active participants was 34 years for women and 37 years for partners, with a mean of 3.5 (1-19) previous pregnancy losses. Rates of obesity, BMI>30 (maternal: 23.8%, paternal: 22.4%), smoking (maternal:7.4%, paternal: 19.4%) and alcohol consumption (maternal: 50%, paternal: 79.2%) were high and 55% of participants were not taking folic acid.Outcome measuresBiannual collection of pregnancy outcomes (ongoing pregnancy, live birth, still birth, pregnancy loss prior to 24 weeks), either through prompted self-reporting, or existing hospital systems.Results639 (82%) women were followed up. 404 reported conception and 106 reported no pregnancy, at least 6 months following registration. Of those that conceived, 72.8% (294/404) had a viable pregnancy. Analysis identified a conception of rate of over 80% and viable pregnancy rate of 60% two years after attending the recurrent miscarriage clinic. 30% of couples had potentially modifiable risk factors for miscarriage.ConclusionsTommy’s Net provides a secure electronic repository on data for couples with recurrent pregnancy loss and associated outcomes. The study identified that subfertility, as well as repeated miscarriage, contributed to failure to achieve live birth. Study findings can enable comparison of clinic management strategies and inform the development of a personalized holistic care package.FunderTommy’s CharitySponsorUniversity Hospitals Coventry and Warwickshire (UHCW) NHS TrustTrial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN) Registry ISRCTN17732518; https://doi.org/10.1186/ISRCTN17732518EthicsApproval from West Midlands-South Birmingham Regional Ethics Committee IRAS No: 213740, 2225751 REC Ref: 17/WM/0050: 17/WM/208Strengths and Limitations of this study (related to the method)The ‘Tommy’s Net’ e-repository and associated database contains baseline and prospective pregnancy outcome data from the largest known population of couples with recurrent miscarriage in the UK.Time to conception and viable pregnancy can be calculated from this data using time to event analysis.Obtaining follow up data is challenging but can be improved by using a variety of data collection methods.Follow up data is only requested biannually, therefore this is an inevitable lag in data collection.Limited use of the English language can be a barrier for participants completing the initial lengthy questionnaire.Key points20% of this recurrent miscarriage population do not conceive and two years after first consultation 40% have not had a viable pregnancy. Early identification of this group could help facilitate early referral to fertility services or targeted research.Miscarriage is physically and psychologically challenging. Some couples may decide not to try to conceive again because of this. Ensuring appropriate psychological support is essential.Preconception care is inadequate. Over one third of couples attend their initial consultation with modifiable risk factors known to impact on miscarriage. Tackling these should be a priority.Having a BMI over 30 and being a smoker is more common within this cohort in women that do not conceive. Targeting of these risk factors may improve conception rate.

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