-
American Journal of Obstetrics and... Dec 2023To evaluate the efficacy of vaginal progesterone for the prevention of preterm birth and adverse perinatal outcomes in twin gestations. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy of vaginal progesterone for the prevention of preterm birth and adverse perinatal outcomes in twin gestations.
DATA SOURCES
MEDLINE, Embase, LILACS, and CINAHL (from their inception to January 31, 2023), Cochrane databases, Google Scholar, bibliographies, and conference proceedings.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials that compared vaginal progesterone to placebo or no treatment in asymptomatic women with a twin gestation.
METHODS
The systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was preterm birth <34 weeks of gestation. Secondary outcomes included adverse perinatal outcomes. Pooled relative risks with 95% confidence intervals were calculated. We assessed the risk of bias in each included study, heterogeneity, publication bias, and quality of evidence, and performed subgroup and sensitivity analyses.
RESULTS
Eleven studies (3401 women and 6802 fetuses/infants) fulfilled the inclusion criteria. Among all twin gestations, there were no significant differences between the vaginal progesterone and placebo or no treatment groups in the risk of preterm birth <34 weeks (relative risk, 0.99; 95% confidence interval, 0.84-1.17; high-quality evidence), <37 weeks (relative risk, 0.99; 95% confidence interval, 0.92-1.06; high-quality evidence), and <28 weeks (relative risk, 1.00; 95% confidence interval, 0.64-1.55; moderate-quality evidence), and spontaneous preterm birth <34 weeks of gestation (relative risk, 0.97; 95% confidence interval, 0.80-1.18; high-quality evidence). Vaginal progesterone had no significant effect on any of the perinatal outcomes evaluated. Subgroup analyses showed that there was no evidence of a different effect of vaginal progesterone on preterm birth <34 weeks of gestation related to chorionicity, type of conception, history of spontaneous preterm birth, daily dose of vaginal progesterone, and gestational age at initiation of treatment. The frequencies of preterm birth <37, <34, <32, <30, and <28 weeks of gestation and adverse perinatal outcomes did not significantly differ between the vaginal progesterone and placebo or no treatment groups in unselected twin gestations (8 studies; 3274 women and 6548 fetuses/infants). Among twin gestations with a transvaginal sonographic cervical length <30 mm (6 studies; 306 women and 612 fetuses/infants), vaginal progesterone was associated with a significant decrease in the risk of preterm birth occurring at <28 to <32 gestational weeks (relative risks, 0.48-0.65; moderate- to high-quality evidence), neonatal death (relative risk, 0.32; 95% confidence interval, 0.11-0.92; moderate-quality evidence), and birthweight <1500 g (relative risk, 0.60; 95% confidence interval, 0.39-0.88; high-quality evidence). Vaginal progesterone significantly reduced the risk of preterm birth occurring at <28 to <34 gestational weeks (relative risks, 0.41-0.68), composite neonatal morbidity and mortality (relative risk, 0.59; 95% confidence interval, 0.33-0.98), and birthweight <1500 g (relative risk, 0.55; 95% confidence interval, 0.33-0.94) in twin gestations with a transvaginal sonographic cervical length ≤25 mm (6 studies; 95 women and 190 fetuses/infants). The quality of evidence was moderate for all these outcomes.
CONCLUSION
Vaginal progesterone does not prevent preterm birth, nor does it improve perinatal outcomes in unselected twin gestations, but it appears to reduce the risk of preterm birth occurring at early gestational ages and of neonatal morbidity and mortality in twin gestations with a sonographic short cervix. However, more evidence is needed before recommending this intervention to this subset of patients.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Progesterone; Premature Birth; Birth Weight; Administration, Intravaginal; Cervix Uteri; Infant, Very Low Birth Weight
PubMed: 37196896
DOI: 10.1016/j.ajog.2023.05.010 -
BJOG : An International Journal of... Oct 2023Evidence for progestogen maintenance therapy after an episode of preterm labour (PTL) is contradictory. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Evidence for progestogen maintenance therapy after an episode of preterm labour (PTL) is contradictory.
OBJECTIVES
To assess effectiveness of progestogen maintenance therapy after an episode of PTL.
SEARCH STRATEGY
An electronic search in Central Cochrane, Ovid Embase, Ovid Medline and clinical trial databases was performed.
SELECTION CRITERIA
Randomised controlled trials (RCT) investigating women between 16 and 37 weeks of gestation with an episode of PTL who were treated with progestogen maintenance therapy compared with a control group.
DATA COLLECTION AND ANALYSIS
Systematic review and meta-analysis were conducted. The primary outcome was latency time in days. Secondary neonatal and maternal outcomes are consistent with the core outcome set for preterm birth studies. Studies were extensively assessed for data trustworthiness (integrity) and risk of bias.
MAIN RESULTS
Thirteen RCT (1722 women) were included. Progestogen maintenance therapy demonstrated a longer latency time of 4.32 days compared with controls (mean difference [MD] 4.32, 95% CI 0.40-8.24) and neonates were born with a higher birthweight (MD 124.25 g, 95% CI 8.99-239.51). No differences were found for other perinatal outcomes. However, when analysing studies with low risk of bias only (five RCT, 591 women), a significantly longer latency time could not be shown (MD 2.44 days; 95% CI -4.55 to 9.42).
CONCLUSIONS
Progestogen maintenance therapy after PTL might have a modest effect on prolongation of latency time. When analysing low risk of bias studies only, this effect was not demonstrated. Validation through further research, preferably by an individual patient data meta-analysis is highly recommended.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Progestins; Tocolytic Agents; Obstetric Labor, Premature; Premature Birth; Birth Weight
PubMed: 37077041
DOI: 10.1111/1471-0528.17499 -
Archives of Gynecology and Obstetrics Jan 2024The immune system is influenced by many factors, including female sex hormones. The extent of this influence, however, is not completely understood so far. This... (Review)
Review
PURPOSE
The immune system is influenced by many factors, including female sex hormones. The extent of this influence, however, is not completely understood so far. This systematic literature review aims at giving an overview of the existing concepts on how endogenous progesterone influences the female immune system along the menstrual cycle.
METHODS
The inclusion criteria were healthy female subjects in their reproductive age with a regular menstrual cycle. The exclusion criteria were exogenous progesterone, animal models, nonhealthy study populations and pregnancy. This led to 18 papers covered in this review. The search was performed using the databases EMBASE, Ovid MEDLINE and Epub, and the last search was conducted on September 18, 2020. Our findings were analyzed in four categories: cellular immune defense, humoral immune defense, objective and subjective clinical parameters.
RESULTS
We demonstrated that progesterone acts in an immunosuppressive way, favoring a Th-2-like cytokine profile. Further, we showed that progesterone inhibits mast cell degranulation and relaxes smooth muscle cells. Furthermore, we found supporting evidence for a so-called window of vulnerability after ovulation, where immune functions are lowered and mediated through progesterone.
CONCLUSION
The clinical relevance of these findings is not completely understood yet. As the sample sizes of included studies were rather small and the content of them was broad, further investigations are needed to define to which extent the described changes actually clinically meaningful, whether they are capable of influencing the female health and how these findings can be used to increase well-being.
Topics: Female; Humans; Immune System; Menstrual Cycle; Ovulation; Progesterone; Reproduction
PubMed: 36933040
DOI: 10.1007/s00404-023-06996-9 -
Archives of Gynecology and Obstetrics Oct 2023Endometrial premalignancies are among the common reasons for outpatient gynecology visits among women in reproductive ages. Due to the continued increase in global... (Review)
Review
PURPOSE
Endometrial premalignancies are among the common reasons for outpatient gynecology visits among women in reproductive ages. Due to the continued increase in global obesity incidence among them, endometrial malignancies are expected to become even further prevalent. Hence, fertility-sparing interventions are essential and needed. In this semi-systematic literature review, we aimed to investigate the role of hysteroscopy in fertility preservation in endometrial cancer and atypical endometrial hyperplasia. Our secondary goal is to analyze the pregnancy outcomes following fertility preservation.
METHODS
We conducted a computed search in PubMed. We included original research articles including hysteroscopic interventions in pre-menopausal patients with endometrial malignancies and premalignancies who underwent fertility-preserving treatments. We collected data on medical treatment, response, pregnancy outcomes, and hysteroscopy.
RESULTS
Of the query results (n = 364), our final analysis included 24 studies. Overall, 1186 patients with endometrial premalignancies and endometrial cancer (EC) were included. More than half of the studies were retrospective design. They included almost ten different forms of progestins. Of the reported pregnancies (n = 392), the overall pregnancy rate was 33.1%. The majority of the studies used operative hysteroscopy (87.5%). Only three (12.5%) reported their hysteroscopy technique in detail. Although more than half of the studies did not provide any information on adverse effects due to hysteroscopy, there were no serious adverse effects among the reported ones.
CONCLUSION
Hysteroscopic resection may increase the success rate of fertility-preserving treatment of EC and atypical endometrial hyperplasia. The clinical significance of the theoretical concern of the dissemination of cancer is not known. Standardization of the use of hysteroscopy in fertility-preserving treatment is needed.
Topics: Pregnancy; Female; Humans; Endometrial Hyperplasia; Fertility Preservation; Hysteroscopy; Retrospective Studies; Endometrial Neoplasms; Uterine Neoplasms
PubMed: 36807742
DOI: 10.1007/s00404-023-06960-7 -
Minerva Obstetrics and Gynecology Dec 2023Despite the many unknowns about its exact mechanism, progesterone and progestins are being successfully used to prevent luteinizing hormone (LH) surge during ovarian... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Despite the many unknowns about its exact mechanism, progesterone and progestins are being successfully used to prevent luteinizing hormone (LH) surge during ovarian stimulation for assisted reproductive technology (ART). We will review progestin primed ovarian stimulation (PPOS) protocols in comparison with gonadotropin releasing hormone (GnRH) analogues and each other.
EVIDENCE ACQUISITION
MEDLINE via PubMed; Cochrane Central Register of Controlled Trials (CENTRAL); Scopus; Web of Science were screened with keywords related to assisted reproductive technology, ovarian stimulation progesterone, GnRH analogue and progesterone in several combinations. Search period was from the date of inception of each database until 20 May 2022.
EVIDENCE SYNTHESIS
Live birth or ongoing pregnancy rate per embryo transfer (ET) was similar in PPOS and GnRH antagonist cycles (RR=1.16, 95% CI: 0.93-1.44). Clinical pregnancy rate per ET was likewise similar (RR=1.12, 95% CI: 0.92-1.37). Miscarriage rate per pregnancy was similar with PPOS and GnRH antagonists in autologous cycles (RR=1.01, 95% CI: 0.65-1.55). Pooled analyses showed similar live birth rate between progestins and short GnRH agonist protocols (RR=1.01, 95% CI: 0.49-2.09), however, clinical pregnancy rates per ET were significantly higher with progestins (RR=1.31, 95% CI: 1.06-1.62). Miscarriage rate per pregnancy was similar with progestins (RR=0.82, 95% CI: 0.55-1.21).
CONCLUSIONS
Progestins seem to be an efficient option for pituitary suppression during ovarian suppression, providing similar outcomes for stimulation and pregnancy. They can be especially beneficial for women for whom fresh ET is not considered.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Ovulation Induction; Progesterone; Progestins
PubMed: 36193835
DOI: 10.23736/S2724-606X.22.05176-4 -
Archives of Gynecology and Obstetrics Aug 2023To investigate the optimal route of progesterone administration for luteal phase support in a frozen embryo transfer. (Review)
Review
OBJECTIVE
To investigate the optimal route of progesterone administration for luteal phase support in a frozen embryo transfer.
DESIGN
Systematic review.
PATIENTS
Women undergoing frozen embryo transfer (FET).
INTERVENTIONS
We conducted an extensive database search of Medline (PubMed), Embase, Web of Science, and Cochrane Trials Register using relevant keywords and their combinations to find randomized controlled trials (RCTs) comparing the routes (i.e., oral, vaginal, intramuscular) of progesterone administration for luteal phase support (LPS) in artificial FET.
MAIN OUTCOME MEASURES
Clinical pregnancy, live birth, miscarriage.
RESULTS
Four RCTs with 3245 participants undergoing artificial endometrial preparation (EP) cycles during FET were found to be eligible. Four trials compared vaginal progesterone with intramuscular progesterone and two trials compared vaginal progesterone with oral progesterone. One study favored of vaginal versus oral progesterone for clinical pregnancy rates (RR 0.45, 95% CI 0.22-0.92) and other study favored intramuscular versus vaginal progesterone for clinical pregnancy rates (RR 1.46, 95% CI 1.21-1.76) and live birth rates (RR 1.62, 95% CI 1.28-2.05). Tabulation of overall evidence strength assessment showed low-quality evidence on the basis that for each outcome-comparison pair, there were deficiencies in either directness of outcome measurement or study quality.
CONCLUSION
There was little consensus and evidence was heterogeneous on the optimal route of administration of progesterone for LPS during FET in artificial EP cycles. This warrants more trials, indirect comparisons, and network meta-analyses.
PROPERO NO
CRD42021251017.
Topics: Pregnancy; Female; Humans; Progesterone; Luteal Phase; Lipopolysaccharides; Embryo Transfer; Pregnancy Rate
PubMed: 35943567
DOI: 10.1007/s00404-022-06674-2 -
American Journal of Perinatology Jan 2024This study aimed to assess vaginal progesterone's effect on different populations and performed comparation between women with varied risk factors. Embase, PubMed,... (Meta-Analysis)
Meta-Analysis
This study aimed to assess vaginal progesterone's effect on different populations and performed comparation between women with varied risk factors. Embase, PubMed, Cochrane library (CENTRAL) were searched without restriction to language up to February 25, 2021. Randomized controlled trials (RCTs) assessing vaginal progesterone administered to women at risk of preterm birth at <37 weeks. Two reviewers independently extracted data, and pooled relative risk (RR) with 95% confidence intervals (CIs) was calculated as well. Women with short cervix have a significantly lower risk of preterm birth at <34 weeks (pooled RR = 0.65; 95% CI: 0.55-0.77; = 0; < 0.001; nine studies) and some neonatal morbidities; interaction tests showed that effect of vaginal progesterone differs significantly between women with short cervix and those with other risk factors (history of preterm birth, exclusive twin gestation, and vaginal bleeding). Evidences of this study showed that singleton gestations, as well as women with short cervix, benefit from vaginal progesterone in preventing preterm birth at <34 weeks and some neonatal morbidities. Women with short cervix are populations who benefit the most among other risk populations. KEY POINTS: · Vaginal progesterone reduces preterm birth and neonatal morbidities.. · Vaginal progesterone effects on some specific populations.. · Women with short cervix benefit the most..
Topics: Female; Humans; Infant, Newborn; Pregnancy; Administration, Intravaginal; Cervix Uteri; Morbidity; Premature Birth; Progesterone; Vagina
PubMed: 35709736
DOI: 10.1055/a-1877-5827