scholarly journals Meta-analysis and randomized controlled studies: what clinicists should know to prevent regular and spontaneous miscarriages of unexplained genesis?

2021 ◽  
pp. 39-44
Author(s):  
Paul Piette
Keyword(s):  
Early Pregnancy ◽  
Recurrent Miscarriage ◽  
Meta Analysis ◽  
First Trimester ◽  
Recommended Treatment ◽  
Randomized Controlled Studies ◽  
History Of ◽  
Threatened Abortion ◽  
The Moment ◽  
Micronized Progesterone

The etiopathology of recurrent miscarriage is a combination of various factors, including chromosomal defects, genetic or structural abnormalities, endocrine abnormalities, infections, immune dysfunction, thrombophilia disorders, antiphospholipid syndrome, and unexplained causes.It has long been known that progesterone is needed to maintain pregnancy and its physiological development. Insufficient progesterone secretion and its low level in the blood serum in early pregnancy is associated with the threat of miscarriage and loss of pregnancy at a later stage – up to 16 weeks of gestation. The effectiveness of the vaginal micronized progesterone (VMP) at a dose of 400 mg twice a day in the first trimester of pregnancy was evaluated in two recent large high-quality multicenter placebo-controlled studies, one of which included pregnant women with recurrent miscarriages of unexplained origin (PROMISE Trial), and the other study included women with early pregnancy loss (PRISM Trial). A key finding, pioneered in the PROMISE study and later confirmed in the PRISM study, was that VMP treatment associated with an increase in live births in line with the number of previous miscarriages. It has been shown that there is no evidence regarding safety concerns with natural micronized progesterone. Treatment with an VMP should be recommended for women with bleeding in early pregnancy and a history of one or more miscarriages. The recommended treatment regimen is 400 mg 2 times a day (800 mg/day) intravaginal, starting from the moment bleeding is detected up to 16 weeks of pregnancy.In the future, there remains uncertainty effectiveness and safety of alternative progestogens (dydrogesterone) for the treatment of women at high risk of threatened abortion and recurrent miscarriage. It is important that dydrogesterone is a synthetic progestin, its structure is significantly different from natural progesterone, and therefore it is necessary to unequivocally prove the short- and long-term safety of this drug before considering its use in clinical practice.

Progestogens for treatment and prevention of pregnancy disorders

2010 ◽  
Vol 3 (3) ◽  
Author(s):  
Adolf E. Schindler
Keyword(s):  
Premature Birth ◽  
Previous History ◽  
First Trimester ◽  
Study Groups ◽  
Treatment And Prevention ◽  
Maternal Immune System ◽  
Hydroxyprogesterone Caproate ◽  
History Of ◽  
Threatened Abortion ◽  
In Pregnancy

AbstractProgesterone appears to be the dominant hormone not only establishing a proper secretory endometrial development but also adequate decidualization to establish pregnancy and sustain pregnancy development. Progesterone is the natural immunoregulator to control the maternal immune system and not to reject the allogeneic fetus. There are two sources of progesterone: corpus luteum first and placenta later. Three progestogens can be used in pregnancy: (i) progesterone (per os, intravaginal and intramuscular), (ii) dydrogesterone (per os), and (iii) 17α-hydroxyprogesterone caproate (intramuscular). There are three indications, for which these progestogens can be clinically used either for treatment or prevention: (i) first trimester threatened and recurrent (habitual) abortion, (ii) premature labor/premature birth, and (iii) pre-eclampsia (hypertension in pregnancy). The available data are limited and only partially randomized. In threatened abortion the use of progesterone, dydrogesterone and 17α-hydroxyprogesterone caproate leads to a significant improved outcome, when at the time of threatened abortion a viable fetus has been ascertained by ultrasound. For prevention of recurrent abortion there are also some data indicating a significant effect compared with women without progestogen treatment. Prevention of preterm birth by progestogens (progesterone vaginally, orally and 17α-hydroxyprogesterone caproate intramuscularly) was significantly effective. The main study groups include pregnant women with a previous history of premature birth. However, also in women with shortened cervix use of progesterone seems to be helpful. The studies done so far in women with risk factors for pre-eclampsia or established pre-eclampsia were based on parenteral progesterone application. However, new studies are urgently needed.

Association of serum progesterone level and endometrial estradiol & progesterone receptors in women with unexplained recurrent miscarriage

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Ihab Found Alam ◽  
Sherif Ahmed Ashoush ◽  
Ihab Adel Gomaa ◽  
Ahmed Sabry AbdEl-Hafeez
Keyword(s):  
Menstrual Cycle ◽  
Recurrent Miscarriage ◽  
Progesterone Receptors ◽  
First Trimester ◽  
Endometrial Biopsy ◽  
Serum Progesterone ◽  
Normal Endometrium ◽  
History Of ◽  
Unexplained Recurrent Miscarriage

Abstract This study investigated the endometrial tissue to study the fluctuation of estrogen receptors (ERs) and progesterone receptors (PRs) in women with recurrent miscarriage compared with normal endometrium of fertile women. Forty women were divided into two groups: 20 non-pregnant women with history of recurrent miscarriage (who had three or more first- trimester miscarriages) and 20 controls. Both groups had regular ovulatory menses and proven fertility. Endometrial biopsy was taken in the two groups during the luteal phase of the menstrual cycle, between the 8th and the 10th postovulatory days using an endometrial biopsy curette for determination of estrogen (E2) and progesterone (P4) hormones levels and their receptors. On the same day as the biopsy, a blood sample was taken for determination of estradiol (E2) and progesterone (P4) levels. The obtained results showed no significant differences between both groups regarding age, BMI, menarche, menstrual cycle & menstruation, significant decrease in E2 and P4 levels in the serum and endometrial biopsy of recurrent miscarriage women versus control. In control and recurrent miscarriage; ER levels in cytoplasm and salt extracted nucleus were higher than PR levels. ER and PR values were higher in the nuclear compartment than in the cytoplasmic compartment. The women with early recurrent miscarriage showed lower levels of both ER and PR significantly. All types of endometrial receptors (ER &PR) and hormones (E2 &P4) in serum and endometrium showed correlation relating to number of previous miscarriages.

O-140 Uterine septum: clinical implications on fertility and obstterics outcomes. A systematic review and meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
G Spagnol ◽  
G Bonaldo ◽  
M Marchetti ◽  
A Vitagliano ◽  
A S Laganà ◽  
...  
Keyword(s):  
Systematic Review ◽  
Birth Rate ◽  
Recurrent Miscarriage ◽  
Meta Analysis ◽  
Live Birth Rate ◽  
Reproductive Outcomes ◽  
Septate Uterus ◽  
History Of ◽  
Uterine Septum ◽  
Infertile Patients

Abstract Study question How does the septate uterus and his metroplasty influence pregnancy rate (PR), live birth rate (LBR), spontaneous abortion rates (SA) and preterm labour rates (PL)? Summary answer Uterine septum is associated with a poor reproductive outcome. Metroplasty reduce the rate of SA but non-conclusive evidence can be extrapolated about PR and PL. What is known already Different studies evaluated the correlation between uterine septum and reproductive outcomes. On one hand, studies reported its association with poor obstetrics outcomes. On the other hand, recent studies raised doubts about the effectiveness of septum metroplasty to improve reproductive outcomes, although recent position papers continue to propose metroplasty in patients with a septate uterus and a history of infertility or miscarriages. Debate is still ongoing on reproductive outcomes of uterine septum on infertile patients and especially on patients with recurrent miscarriage, leading to an unanswered question whether or not these women should be treated. Study design, size, duration Systematic review and meta-analysis of published studies that evaluated the clinical impact of uterine septum and its metroplasty on reproductive and obstetrics outcomes. The meta-analysis included study with infertile patients or patients with a history of recurrent miscarriage. Searches were conducted using the following search terms: uterine septum, septate uterus, metroplasty, pregnancy rate, live birth rate, spontaneous miscarriage, infertility, preterm delivery. Primary outcomes were PR and LBR. Secondary outcomes were SA and PL. Participants/materials, setting, methods The meta-analysis was written following the PRISMA guidelines. Fifty-nine full-text articles were preselected based on title and abstract. Endpoints were evaluated in three subgroups: 1) infertile/recurrent miscarriage patients with septum versus no septum 2) infertile/recurrent miscarriage patients with treated versus untreated septum 3) infertile/recurrent miscarriage patients before-after septum removal. Odds-ratios (OR) with 95% confidence intervals (CI) were calculated for outcome measures. Random-effect meta-analysis was performed and a p-value less than 0.05 was considered statistically significant. Main results and the role of chance Data from 37 articles were extracted. In the first subgroup (10 studies), a lower PR and LBR were associated with septate uterus vs. controls, respectively (OR 0.39, 95% CI 0.26 to 0.58; p < 0.000; low-heterogeneity and OR 0.21, 95% CI 0.12 to 0.39; p < 0.0001; small-heterogeneity) and a higher proportion of SA and PL was associated with septate uterus vs. controls, respectively (OR 4.17, 95% CI 2.83 to 6.15; p < 0.000; moderate-heterogeneity and OR 2.18, 95% CI 1.27 to 3.76; p = 0.005; low-heterogeneity). In the second subgroup (8 studies), PR and PL were not different in removed vs. unremoved septum, respectively (OR 1.10, 95% CI 0.49 to 2.49; p = 0.82; moderate heterogeneity and OR 0.44, 95% CI 0.18 to 1.08; p = 0.08;low-heterogeneity) and a lower proportion of SA was associated with removed vs. unremoved septum (OR 0.40, 95% CI 0.17 to 0.95; p = 0.001; substantial-heterogeneity). In the third subgroup (19 studies), the proportion of LBR was higher after the removal of septum (OR 49.58, 95% CI 29.93 to 82.13; p < 0.0001; moderate-heterogeneity) and the proportion of SA and PL was lower after the removal of septum, respectively (OR 0.02, 95% CI 0.02 to 0.04; p < 0.000; moderate-heterogeneity and OR 0.05, 95% CI 0.03 to 0.08; p = <0.000; low-heterogeneity). Limitations, reasons for caution The present meta-analysis is limited by the observational design of included studies because, in literature, there are no prospective randomized controlled trials (RCTs). In the second and third subgroup of analysis clinical heterogeneity within and between studies represents another limitation. Wider implications of the findings The results of this meta-analysis confirm the detrimental effect of uterine septum on PR, LBR, SA and PL. Its treatment seems to reduce the rate of SA. Metroplasty should still be considered as good clinical practice in patients with a history of infertility and recurrent abortion. Trial registration number Not applicable © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: [email protected].

P–426 Uterine Natural Killer Cells in Recurrent Miscarriage and Implantation Failure: An Updated Systematic Review and Meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E V Woon ◽  
O Greer ◽  
N Shah ◽  
V Male ◽  
M Johnson
Keyword(s):  
Systematic Review ◽  
Nk Cells ◽  
Early Pregnancy ◽  
Subgroup Analysis ◽  
Recurrent Miscarriage ◽  
Meta Analysis ◽  
Implantation Failure ◽  
Significant Difference ◽  
Uterine Nk Cells ◽  
Definition Of

Abstract Study question Do women with recurrent miscarriage (RM) or implantation failure (RIF) have different levels of uterine Natural Killer (NK) cells compared to fertile controls? Summary answer Women with RIF but not RM are associated with significantly higher levels of CD56+ uterine NK cells compared to controls. What is known already Uterine NK cells (uNK) are different from peripheral NK cells (pNK) and are important in early pregnancy for development of the placenta. The association between uNK and RM/RIF is less clear, but dysfunction of uNK is believed to result in early pregnancy failure. Previous systematic reviews by Seshadri (2014) and Tang (2013) on infertile and RM patients showed no significant difference in uNK levels and highlighted need for further studies. Since, many prospective studies have been published and therefore warrant an updated systematic review. On the other hand, evidence for correlation between uNK and pNK is sparse and needs clarification. Study design, size, duration We have conducted a systematic review and meta-analysis to evaluate three outcomes. The primary outcome was the difference of uNK level in RM/RIF compared to controls. The secondary outcome was livebirth rate in women with RM/RIF with high compared to normal uNK level, and the tertiary outcome was correlation between uNK and pNK in RM/RIF. Participants/materials, setting, methods The electronic database search included MEDLINE, EMBASE, Web of Science and bibliographies from included articles from inception to December 2020 using a combination of MESH and keywords. Search, screen, and data extraction were performed by two reviewers independently. Quality assessment was conducted with ROBINS-I and meta-analysis with Revman 5.3. Out of 4636 studies screened, 43 studies (2539 women) and 3 studies each (598 and 77 women) were analysed for primary, secondary and tertiary outcomes respectively. Main results and the role of chance Our meta-analysis showed that CD56+ uNK were significantly higher in women with RIF but not RM compared to controls (SMD 0.60; 95% CI 0.12–1.08]. Subgroup analysis in RM patients showed no significant difference whether definition of 2 or 3 previous RM was used, in primary/secondary RM compared to controls, or in primary versus secondary RM. CD56+ uNK were significantly higher in RM/RIF when sampled during mid-luteal phase [SMD 0.56; 95% CI 0.19–0.93] but not in the early pregnancy decidua. Interestingly, there was significant difference in CD56+ uNK when analysed by immunohistochemistry [SMD 0.50; CI 0.05–0.94] but not by flow cytometry, and when CD56+ uNK were reported as percentage over total endometrial cells [SMD 0.58; 95% CI 0.10–1.07]. Further subgroup analysis showed significant difference in CD16 + [SMD 0.54; 95% CI 0.18–0.89] but not in CD56+CD16-, CD56+CD16+ or CD57. For pregnancy outcome, there was no significant difference in livebirth rate in RM/RIF patients with high uNK compared to normal uNK [RR 1.06, 95% CI 0.86–1.30]. Mean uNK level in RM patients with subsequent miscarriage was not significantly higher than subsequent livebirth. Finally, the pooled correlation between CD56 pNK and CD56 uNK (r = 0.42; 95% CI –0.04–0.73] was not significant in RM/RIF patients. Limitations, reasons for caution The meta-analysis is limited by quality of some of the studies. Some data were presented in median that was transformed to mean which may result in data skew. Other confounding factors e.g. maternal age, fetal karyotype, number of previous miscarriages and variable definition of controls may contribute to bias. Wider implications of the findings: Clinical interpretation of uNK level needs to be treated with caution because there is significant heterogeneity in method of analysis. There may be a role for uNK measurement in RIF patients however further studies to understand pathophysiology underlying elevated uNK is warranted before recommending it as a diagnostic tool. Trial registration number N/A

scholarly journals Incidence of early pregnancy complications, management protocols and its outcome in patients at Gujarat Adani Institute of Medical Science, Bhuj, Kutch, Gujarat, India

2017 ◽  
Vol 6 (9) ◽  
pp. 3837
Author(s):  
Akansha . ◽  
Nagajan Bhadarka
Keyword(s):  
Ectopic Pregnancy ◽  
Early Pregnancy ◽  
Pregnancy Complications ◽  
Medical Science ◽  
First Trimester ◽  
Related Complication ◽  
Hospital Patients ◽  
Clinical Benefits ◽  
Threatened Abortion ◽  
Vesicular Mole

Background: Early Pregnancy Complications can cause significant morbidity and mortality. Pregnant women an present with h/o amenorrhea, abdominal pain, vaginal bleeding or incidental scan finding of missed abortion, ectopic pregnancy and vesicular mole, features of hypermesis gravidorum like fatigue, nausea, vomiting, dryness and diminished urine output. The objective of present study was to analyze the incidence of various early pregnancy complications, assess the protocols for diagnosing these complications and their management.Methods: Present study was conducted at the Department of Obstetrics and Gynecology, Gujarat Adani Institute of Medical Science, Bhuj, Kutch, Gujarat. All the women with first trimester pregnancy with different complications were included in this study while those women with uneventful first trimester were excluded. The inducted women were registered on pre-designed proforma. Studied variables including demographic details, gestational period, type of complications, risk factors, treatment and outcome.Results: Out of 740 total admissions 439 abortions of which incomplete abortion was 262, missed abortions were 132, threatened abortion 42 and 3 cases of septic abortion, ectopic pregnancy 154, molar pregnancy33, hyperemesis 31. There were about 63 cases of non-pregnancy related complication reported during early pregnancy like 31 with UTI, 9 with renal colic, 2 cases of appendicitis, four cases of asymptomatic cholelithiasis, 2 cases of hepatitis, 5 cases of ovarian cyst complicating pregnancy, 2 cases of ovarian torsion. Their mean age was 30.8+6.8 years.Conclusions: Study was successful in creating a confidence among trainees when following the recommended protocols as well as delivering clinical benefits to the hospital, patients and staff. Early gynecological consultation and bedside ultrasound scanning within the emergency department were key requirements for any emergency concerns.

scholarly journals A study of feto-maternal outcome in bleeding per vaginum in first trimester of pregnancy

2020 ◽  
Vol 9 (3) ◽  
pp. 1191
Author(s):  
Jaydeep J. Bhatu ◽  
Darshil S. Prajapati
Keyword(s):  
Vaginal Bleeding ◽  
Local Population ◽  
Previous History ◽  
Perinatal Outcomes ◽  
First Trimester ◽  
Maternal Complications ◽  
History Of ◽  
Threatened Abortion ◽  
Degree Of Association ◽  
In Pregnancy

Background: Bleeding per vaginum in the first trimester is a common obstetric entity. Four major causes of pathological bleeding in 1st trimester are miscarriage, ectopic pregnancy, implantation bleeding of pregnancy and cervical pathology. The purpose of this study was to investigate and understand the effect of first trimester vaginal bleeding on maternal and perinatal outcomes in the local population to which our hospital serves. Objective of this study was to estimate the degree of association between first-trimester bleeding and miscarriage, pregnancy outcomes in women with threatened abortion, various maternal complications and outcome of labor in pregnancy complicated by first-trimester bleeding and adverse fetal outcomes affected with first trimester bleeding.Methods: This prospective observational study was carried out on 110 women attending hospital with history of first trimester vaginal bleeding at a tertiary health center - sola civil hospital Ahmedabad for a period of twelve months.Results: Majority (69%) of first trimester bleeding occurs in age group of 21-30 years and majority of patients were primigravida constituting 53% out of 110 patients, 48 patients presented with abortions, out of which 26 had threatened abortion and 22 had other abortions. Primi para with previous history of bleeding per vaginum had more chances to go in full term in present pregnancy.Conclusions: Patients presenting with heavy bleeding per vaginum ended up in pregnancy loss and thus a poor outcome. In the presence of sub-chorionic hematoma, the prognosis of pregnancy is greatly affected as the risk of pre-term, IUGR and especially miscarriages increase significantly.

SIGNIFICANCE OF ULTRASOUND IN CLINICALLY DIAGNOSED CAUSES OF VAGINAL BLEEDING IN FIRST TRIMESTER PREGNANCY

2021 ◽  
pp. 74-75
Author(s):  
Amit Shankhwar ◽  
Prem Siddharth Tripathi ◽  
Saurabh Atram ◽  
Pankaj Kujur ◽  
Prakhar Nigam ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Vaginal Bleeding ◽  
Imaging Modality ◽  
First Trimester ◽  
First Trimester Pregnancy ◽  
Incomplete Abortion ◽  
Trimester Pregnancy ◽  
Highly Sensitive ◽  
History Of ◽  
Threatened Abortion

Background: (1) Nearly one-fourth (20-25%) of all pregnant women present with history of vaginal bleeding during the rst trimester . Ultrasound imaging plays an important role in determining the causes of vaginal bleeding during rst trimester of pregnancy. Aims & Objectives:To evaluate the signicance of ultrasound in clinically diagnosed causes of vaginal bleeding in rst trimester pregnancy. Methods: 100 women with vaginal bleeding during rst trimester of pregnancy with clinical diagnosis were evaluated by ultrasonography [USG] and interpretation was compared. Results: Among these 100 cases, threatened abortion was the commonest cause of bleeding (30%) followed by incomplete abortion. Disparity was found between clinical diagnosis of rst trimester vaginal bleed and ultrasound diagnosis. Ultrasound is highly sensitive and specic in diagnosing all causes of rst trimester vaginal bleed including ectopic pregnancy. Conclusion: With good diagnostic performance, USG proves to be an important imaging modality in determining the causes of vaginal bleeding during rst trimester of pregnancy and thus provides an aid for clinicians in better management of patients.

SIGNIFICANCE OF ULTRASOUND IN CLINICALLY DIAGNOSED CAUSES OF VAGINAL BLEEDING IN FIRST TRIMESTER PREGNANCY

2021 ◽  
pp. 39-40
Author(s):  
Amit Shankhwar ◽  
Prem Siddharth Tripathi ◽  
Saurabh Atram ◽  
Pankaj Kujur ◽  
Prakhar Nigam ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Vaginal Bleeding ◽  
Imaging Modality ◽  
First Trimester ◽  
First Trimester Pregnancy ◽  
Incomplete Abortion ◽  
Trimester Pregnancy ◽  
Highly Sensitive ◽  
History Of ◽  
Threatened Abortion

Background: Nearly one-fourth (20-25%) of all pregnant women present with history of vaginal bleeding during the rst trimester (1). Ultrasound imaging plays an important role in determining the causes of vaginal bleeding during rst trimester of pregnancy. Aims & Objectives: To evaluate the signicance of ultrasound in clinically diagnosed causes of vaginal bleeding in rst trimester pregnancy. Methods: 100 women with vaginal bleeding during rst trimester of pregnancy with clinical diagnosis were evaluated by ultrasonography [USG] and interpretation was compared. Results: Among these 100 cases, threatened abortion was the commonest cause of bleeding (30%) followed by incomplete abortion. Disparity was found between clinical diagnosis of rst trimester vaginal bleed and ultrasound diagnosis. Ultrasound is highly sensitive and specic in diagnosing all causes of rst trimester vaginal bleed including ectopic pregnancy. Conclusion: With good diagnostic performance, USG proves to be an important imaging modality in determining the causes of vaginal bleeding during rst trimester of pregnancy and thus provides an aid for clinicians in better management of patients.

scholarly journals Role of human chorionic gonadotrophin to prevent repeated early pregnancy loss

2016 ◽  
Vol 48 (1-2) ◽  
pp. 7-10
Author(s):  
Eti Saha ◽  
Fouzia Begum ◽  
Zannatul Ferdous Jesmin
Keyword(s):  
Early Pregnancy ◽  
Pregnancy Loss ◽  
First Trimester ◽  
Additional Treatment ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Early Pregnancy Loss ◽  
Significant Difference ◽  
Improve Pregnancy Outcome ◽  
History Of

Early pregnancy loss is a frustrating experience for both the patient and the physician. Approximately 5% of couples trying to conceive have 2 consecutive miscarriages and approximately 1% couples have 3 or more consecutive losses. Objective of this study is to determine whether therapy with dydrogesterone or Human chorionic Gonadotrophin hormone (HCG) in history of repeated pregnancy loss during the first trimester of pregnancy will improve pregnancy outcome. This is a prospective open comparative study.Women having early pregnancy presenting to a private clinic with history of early pregnancy loss, having no medical disorder were included in this study. Eligible subjects were randomised to receive either dydrogesterone 20mg daily or injection Human Chorionic Gonadotrophins (HCG) 5000 iu intramuscularly at 72 hours interval up to fourteen weeks of pregnancy or no additional treatment. Follow up of those patients were done with transabdominal ultrasonography. Hundred women were recruited. There was no statistically significant difference between the three groups with regard to pretreatment status. The continuing pregnancy success rate was higher in women treated with dydrogesterone (79.17%) and highest with Injection Human Chorionic, Gonadotrophin (86.36%) compared with women received no treatment (70%), (p=0.358). Hormonal support with either dydrogesterone or Human Chorionic Gonadotrophin may increase the chances of a successful pregnancy in women with a history of spontaneous abortion.Bang Med J (Khulna) 2015; 48 : 7-10

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