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Reproductive Biology and Endocrinology... Nov 2021Progesterone supplementation is widely performed in women with threatened miscarriage or a history of recurrent miscarriage; however, the effects of early progesterone... (Meta-Analysis)
Meta-Analysis
Pregnancy-related complications and perinatal outcomes following progesterone supplementation before 20 weeks of pregnancy in spontaneously achieved singleton pregnancies: a systematic review and meta-analysis.
BACKGROUND
Progesterone supplementation is widely performed in women with threatened miscarriage or a history of recurrent miscarriage; however, the effects of early progesterone supplementation on pregnancy-related complications and perinatal outcomes in later gestational weeks remain unknown.
METHODS
Ovid MEDLINE, the Cochrane Library, Embase and ClinicalTrials.gov were searched until April 3rd, 2021. Randomized controlled trials regarding spontaneously achieved singleton pregnancies who were treated with progestogen before 20 weeks of pregnancy and were compared with those women in unexposed control groups were selected for inclusion. We performed pairwise meta-analyses with the random-effects model. The risk of bias was assessed according to the Cochrane Collaboration tool. The primary outcomes included preeclampsia (PE), and gestational diabetes mellitus (GDM), with the results presented as odds ratios (ORs) with 95% confidence intervals (CIs).
RESULTS
We identified nine eligible studies involving 6439 participants. The pooled OR of subsequent PE following early progestogen supplementation was 0.64 (95% CI 0.42-0.98, moderate quality of evidence). A lower OR for PE was observed in the progestogen group when the subgroup analysis was performed in the vaginal subgroup (OR 0.62, 95%CI 0.40-0.96). There was insufficient evidence of a difference in the rate of GDM between pregnant women with early progestogen supplementation and unexposed pregnant women (OR 1.02, 95% CI 0.79-1.32, low quality of evidence). The pooled OR of low birth weight (LBW) following oral dydrogesterone was 0.57 (95% CI 0.34-0.95, moderate quality of evidence). The results were affected by a single study and the total sample size of enrolled women did not reach the required information size.
CONCLUSION
Use of vaginal micronized progesterone (Utrogestan) in spontaneously achieved singleton pregnancies with threatened miscarriage before 20 weeks of pregnancy may reduce the risk of PE in later gestational weeks. Among spontaneously achieved singleton pregnancies with threatened miscarriage or a history of recurrent miscarriage, use of oral dydrogesterone before 20 weeks of pregnancy may result in a lower risk of LBW in later gestational weeks. However, the available data were not sufficient to reach definitive conclusions, which highlighted the need for future studies.
Topics: Abortion, Habitual; Dietary Supplements; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Progesterone; Randomized Controlled Trials as Topic
PubMed: 34732210
DOI: 10.1186/s12958-021-00846-6 -
Human Reproduction Update Feb 2022Endometrial cancer is common and usually occurs after menopause, but the number of women diagnosed during reproductive age is increasing. The standard treatment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endometrial cancer is common and usually occurs after menopause, but the number of women diagnosed during reproductive age is increasing. The standard treatment including hysterectomy is effective but causes absolute uterine factor infertility. In order to avoid or postpone surgery, conservative management of endometrial cancer (CMEC) has been proposed for younger women who want to retain their fertility.
OBJECTIVE AND RATIONALE
The main objective of this study was to estimate the chances of pregnancy and live birth for women with early-stage endometrial cancer (EEC) who are managed conservatively for fertility preservation.
SEARCH METHODS
The PRISMA recommendations for systematic reviews and meta-analyses were followed. Structured searches were performed in PubMed, Embase and the Cochrane Library, from inception until 13 June 2021. Inclusion was based on the following criteria: group or subgroup of women with Clinical Stage IA, well-differentiated, endometrioid endometrial cancer (from now on, EEC); CMEC for fertility preservation; and reported frequencies of women achieving pregnancy and/or live birth after CMEC. The following exclusion criteria applied: impossibility to isolate/extract outcome data of interest; second-line CMEC for persistent/recurrent disease; CMEC in the presence of synchronous tumours; case reports; non-original or duplicated data; and articles not in English. Qualitative synthesis was performed by means of tabulation and narrative review of the study characteristics. Study quality was assessed with an ad hoc instrument and several moderator and sensitivity analyses were performed.
OUTCOMES
Out of 1275 unique records, 133 were assessed in full-text and 46 studies were included in the review. Data from 861 women with EEC undergoing CMEC were available. Progestin-based treatment was reported in all but three studies (93.5%; 836 women). Complete response to treatment was achieved in 79.7% of women, with 35.3% of them having a disease recurrence during follow-up. Of 286 pregnancies obtained after CMEC; 69.4% led to live birth (9% of them multiple births) and 66.7% were achieved through fertility treatment. Based on random-effects meta-analyses, women treated with progestin-based CMEC have a 26.7% chance of achieving pregnancy (95% CI 21.3-32.3; I2 = 53.7%; 42 studies, 826 women) and a 20.5% chance to achieve a live birth (95% CI 15.7-25.8; I2 = 40.2%; 39 studies, 650 women). Sample size, average age, publication year, study design and quality score were not associated with the outcomes of progestin-based CMEC in moderator analyses with meta-regression. However, mean follow-up length (in months) was positively associated with the chances of pregnancy (regression coefficient [B] = 0.003; 95% CI 0.001-0.005; P = 0.006) and live birth (B = 0.005; 95% CI 0.003-0.007; P < 0.001). In sensitivity analyses, the highest chances of live birth were estimated in subsets of studies including only women of age 35 or younger (30.7%), the combination of progestins with hysteroscopic resection (30.7%), or at least 3 years of follow-up (42.4%).
WIDER IMPLICATIONS
Progestin-based CMEC is viable for women with well-differentiated, Clinical Stage 1A, endometrioid endometrial cancer who want to preserve their fertility, but there is room for improvement as only one-fifth of them are estimated to achieve live birth according to this meta-analysis. Further investigations on prognosis-driven selection, hysteroscopic resection and long-term surveillance are arguably needed to improve the reproductive outcomes of CMEC.
Topics: Adult; Female; Humans; Pregnancy; Conservative Treatment; Endometrial Neoplasms; Live Birth; Pregnancy Rate; Progestins; Young Adult
PubMed: 34935045
DOI: 10.1093/humupd/dmab041 -
European Journal of Obstetrics,... Aug 2021Increasing incidence of endometrial cancer and late motherhood enhance conservative management in clinical practice. Although different approaches to fertility-sparing...
The results of different fertility-sparing treatment modalities and obstetric outcomes in patients with early endometrial cancer and atypical endometrial hyperplasia: Case series of 30 patients and systematic review.
OBJECTIVE
Increasing incidence of endometrial cancer and late motherhood enhance conservative management in clinical practice. Although different approaches to fertility-sparing treatment are possible, it is still unknown which patients will benefit more from systemic or local treatment. Aim of this paper is to analyze the effectiveness of different methods of conservative management and obstetric outcomes in patients with early endometrial cancer and atypical endometrial hyperplasia.
STUDY DESIGN
30 patients (10 with atypical endometrial hyperplasia, 20 with endometrial cancer) treated conservatively were included to retrospective analysis. 24 patients receiving progestins were divided into 2 groups according to the dose (low and high dose); 6 patients were treated with levonorgestrel releasing intrauterine device. Effectiveness of therapy (complete, partial or absent) and obstetric outcomes (number of pregnancies and live births) were assessed. Electronic databases (MEDLINE, Web of Science, Embase) were searched for articles according to criteria: 1) fertility-sparing treatment of endometrial cancer/atypical endometrial hyperplasia in patients of reproductive age, 2) assessment of pregnancy/obstetric results. The risk of bias was assessed with the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Series.
RESULTS
Complete and partial remission were achieved in 21 and 3 patients, respectively. 6 patients did not respond to treatment. Relapse was diagnosed in 6 patients. Probability of complete remission according to low-, high-dose regimen and levonorgestrel-releasing intrauterine device were 55.6% (46.5%-64.7%), 73.3% (65.2%-81.4%) and 83.3% (76.5%-90.1%) respectively. 4 patients get pregnant and 3 of them born children. 25 studies (21 retrospective, 4 prospective) with 812 participants were included in the systematic review. The most studied was progestin based treatment. Complete and partial response to fertility-sparing management was diagnosed in 634 and 38 patients, respectively. Relapse was diagnosed in 170 patients. Median times of follow-up range from 17 (1-45) to 98 (35-176) months. The total number of pregnancies and live births were 352 and 246, respectively.
CONCLUSIONS
Fertility-sparing treatment is a safe method of management in young women with endometrial cancer/atypical endometrial hyperplasia. While the main goal of conservative management is preserving the possibility of having children, only a small number of women will become pregnant and give birth.
Topics: Child; Child, Preschool; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Neoplasm Recurrence, Local; Pregnancy; Progestins; Prospective Studies; Retrospective Studies; Treatment Outcome
PubMed: 34214800
DOI: 10.1016/j.ejogrb.2021.06.007 -
Developmental Neuroscience 2023Hypoxic-ischaemic encephalopathy (HIE) in the newborn baby is a major contributor to neonatal mortality and morbidity across the world. Therapeutic hypothermia (TH) is... (Review)
Review
Hypoxic-ischaemic encephalopathy (HIE) in the newborn baby is a major contributor to neonatal mortality and morbidity across the world. Therapeutic hypothermia (TH) is the current standard treatment for moderate to severe HIE, but not all babies benefit. Potential neuroprotective actions of progesterone (PROG) include anti-apoptotic, anti-inflammatory, and anti-oxidative effects and reduction of energy depletion, tissue/cellular oedema, and excitotoxicity. In pre-clinical studies of neonatal HIE, PROG has neuroprotective properties but has not been the subject of systematic review. Here, our objective was to evaluate the evidence base for PROG as a potential therapeutic agent in HIE. The PICO framework was used to define the following inclusion criteria. Population: human neonates with HIE/animal models of HIE; intervention: PROG +/- other agents; comparison: V.S. control; outcome: pathological, neurobehavioural, and mechanistic outcome measures. Medline, EMBASE, and CINHAL were then searched between August to October 2018 using pre-defined medical subject heading and keywords. Study inclusion, data extraction, and risk of bias (ROB) analysis using the SYRCLE ROB tool were carried out by two authors. 14 studies were included in the review. They typically displayed a high ROB. This systematic review suggests that PROG reduced neuropathology and reduced neurobehavioural deficits post-hypoxic-ischaemic (HI) insult in 8 and 3 studies, respectively. However, there was sex dimorphism in the effects of PROG. In addition, there are limitations and biases in these studies, and there remains a need for well-designed large pre-clinical studies with greater methodological quality to further inform the efficacy, safety, dose, timing, and frequency of PROG administration. With such data, large animal studies could be planned combining PROG administration with and without TH.
Topics: Animals; Infant, Newborn; Humans; Neuroprotective Agents; Hypoxia-Ischemia, Brain; Progesterone; Hypothermia, Induced; Neuroprotection
PubMed: 36436500
DOI: 10.1159/000521540 -
Frontiers in Endocrinology 2022The aim of this systematic review and meta-analysis was to update the current evidence for the efficacy and safety of progesterone luteal phase support (LPS) following... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The aim of this systematic review and meta-analysis was to update the current evidence for the efficacy and safety of progesterone luteal phase support (LPS) following ovarian stimulation and intrauterine insemination treatment (OS-IUI) for unexplained or mild male infertility. Four additional studies were identified compared to the previous review in 2017. Twelve RCTs (2631 patients, 3262 cycles) met full inclusion criteria. Results from quantitative synthesis suggest that progesterone LPS after OS-IUI leads to higher live birth (RR 1.38, 95%CI [1.09, 1.74]; 7 RCTs, n=1748) and clinical pregnancy rates (RR 1.38, 95% CI [1.21, 1.59]; 11 RCTs, n=2163) than no LPS or placebo. This effect is specifically present in protocols using gonadotropins for OS-IUI (RR 1.41, 95%CI [1.17, 1.71]; 7 RCTs, n=1114), and unclear in protocols involving clomiphene citrate (RR 1.01, 95% CI [0.05, 18.94]; 2 RCTs, n=138). We found no effect of progesterone LPS on multiple pregnancy or miscarriage rates. No correlation between drug-dosage or duration of treatment and effect size was seen. Though our results suggest both benefit and safety of progesterone LPS in OS-IUI, evidence is of low to moderate quality and additional well-powered trials are still mandatory to confirm our findings and justify implementation in daily practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=292325, identifier CRD42021292325.
Topics: Clomiphene; Female; Gonadotropins; Humans; Insemination, Artificial; Luteal Phase; Male; Ovulation Induction; Pregnancy; Progesterone
PubMed: 36120470
DOI: 10.3389/fendo.2022.960393 -
Frontiers in Oncology 2022The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients...
BACKGROUND
The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients desiring pregnancy, fertility-sparing treatment (FST) can be adopted. Our review aims to collect the most incisive studies about the possibility of conservative management for patients with grade 2, stage IA EC. Different approaches can be considered beyond demolition surgery, such as local treatment with levonorgestrel-releasing intra-uterine device (LNG-IUD) plus systemic therapy with progestins.
STUDY DESIGN
Our systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, EMBASE, and Scopus databases were consulted, and five studies were chosen based on the following criteria: patients with a histological diagnosis of EC stage IA G2 in reproductive age desiring pregnancy and at least one oncological outcome evaluated. Search imputes were "endometrial cancer" AND "fertility sparing" AND "oncologic outcomes" AND "G2 or stage IA".
RESULTS
A total of 103 patients were included and treated with a combination of LNG-IUD plus megestrol acetate (MA) or medroxyprogesterone acetate (MPA), gonadotrophin-releasing hormone (GnRH) plus MPA/MA, hysteroscopic resectoscope (HR), and dilation and curettage (D&C). There is evidence of 70% to 85% complete response after second-round therapy prolongation to 12 months.
CONCLUSIONS
Conservative measures must be considered temporary to allow pregnancy and subsequently perform specific counseling to adopt surgery. Fertility-sparing management is not the current standard of care for young women with EC. It can be employed for patients with early-stage diseases motivated to maintain reproductive function. Indeed, the results are encouraging, but the sample size must be increased.
PubMed: 36185260
DOI: 10.3389/fonc.2022.965029 -
Menopause (New York, N.Y.) May 2022Long-term sleep disturbances in menopausal women are closely related to cardiovascular disorders, metabolic disorders, and cognitive impairment. At present, hormone... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Long-term sleep disturbances in menopausal women are closely related to cardiovascular disorders, metabolic disorders, and cognitive impairment. At present, hormone therapy (HT) is a standard treatment for menopausal symptoms. However, it remains unclear whether HT can improve sleep quality.
OBJECTIVE
We did a systematic review and meta-analysis to assess the effects of different HT regimens on menopausal sleep quality.
EVIDENCE REVIEW
We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, PsycINFO, CINAHL, and Web of Science for randomized controlled trials of menopausal HT on sleep disturbances up to June 14,2021. Information about ongoing and unpublished trials was collected by searching WHOICTRP and ClinicalTrials.gov. Our primary outcome was sleep quality with objective measurements. We estimated the standardized mean difference (SMD) using random-effects models.
FINDINGS
We identified a total of 3,059 studies and finally included 15 studies in the meta-analysis. Compared with placebo, HT improved self-reported sleep outcomes (SMD = -0.13; 95% CI, -0.18 to -0.08, P < 0.00001 and I2 = 41%), but not sleep parameters measured by polysomnography. Subgroup analyses according to the regimen of HT showed that 17β-estradiol (17β-E2) (SMD = -0.34; 95% CI, -0.51 to -0.17, P < 0.0001, and I2 = 0%) and conjugated equine estrogens (SMD = -0.10; 95% CI, -0.12 to -0.07, P < 0.00001, and I2 = 0%) improved sleep quality. Moreover, transdermal administration (SMD = -0.35; 95% CI, -0.64 to -0.06, and P = 0.02) was more beneficial than oral (SMD = -0.10; 95% CI, -0.14 to -0.07, and P < 0.00001). In addition, the combination of estrogen and progesterone had a positive effect on sleep disturbance (SMD = -0.10; 95% CI, -0.13 to -0.07, P < 0.00001, and I2 = 0%), while estrogen monotherapy did not. The results showed that estrogen/micronized progesterone (SMD = -0.22; 95% CI, -0.37 to -0.06, P = 0.007, and I2 = 0%) and estrogen/medroxyprogesterone acetate (SMD = -0.10; 95% CI, -0.13 to -0.07, P < 0.00001, and I2 = 0%) could alleviate sleep disturbance.
CONCLUSIONS AND RELEVANCE
HT has a beneficial effect on sleep disturbance to some extent, and the formulations and routes of administration of hormonal agents influence the effect size.
Topics: Estrogens; Female; Hormone Replacement Therapy; Humans; Menopause; Progesterone; Sleep Quality
PubMed: 35102100
DOI: 10.1097/GME.0000000000001945 -
Archives of Gynecology and Obstetrics Apr 2024Short-acting progestin-only injectables containing depot medroxyprogesterone acetate (DMPA) are a safe method of contraception. Although DMPA has been available for... (Review)
Review
PURPOSE
Short-acting progestin-only injectables containing depot medroxyprogesterone acetate (DMPA) are a safe method of contraception. Although DMPA has been available for several decades, there is little data on its influence on the risk of breast cancer. Hence, the aim of this paper was to provide an overview of the existing studies and create clarity regarding a possible association with breast cancer.
METHODS
Literature searches were executed in MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and ICTRP. Search terms were related to DMPA and breast cancer. After elimination of duplicates, 3'850 studies were identified and assessed according to inclusion and exclusion criteria. Finally, ten studies were selected and included in this review.
RESULTS
All the selected papers were case-control-studies, except for one pooled analysis and one study comparing observed and expected number of cancer cases. Most of the included studies found no overall elevated breast cancer incidence in DMPA users, only one study found a slightly increased risk and two studies concluded with a significant increase for the overall breast cancer risk.
CONCLUSION
There is little evidence that DMPA may increase the overall risk for breast cancer. However, the incidence of breast cancer is possibly increased in current and more recent users, especially in women younger than 35 years. Long-term use did not result in any risk increase. Nevertheless, further studies will be necessary to confirm these findings and weigh up the individual risks and benefits of this contraceptive method.
Topics: Female; Humans; Medroxyprogesterone Acetate; Delayed-Action Preparations; Breast Neoplasms; Contraceptive Agents, Female; Progestins
PubMed: 37966517
DOI: 10.1007/s00404-023-07265-5 -
Frontiers in Endocrinology 2022To investigate the risk of preterm birth in women with a placenta previa or a low-lying placenta for different cut-offs of gestational age and to evaluate preventive... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the risk of preterm birth in women with a placenta previa or a low-lying placenta for different cut-offs of gestational age and to evaluate preventive interventions.
SEARCH AND METHODS
MEDLINE, EMBASE, CENTRAL, Web of Science, WHO-ICTRP and clinicaltrials.gov were searched until December 2021. Randomized controlled trials, cohort studies and case-control studies assessing preterm birth in women with placenta previa or low-lying placenta with a placental edge within 2 cm of the internal os in the second or third trimester were eligible for inclusion. Pooled proportions and odds ratios for the risk of preterm birth before 37, 34, 32 and 28 weeks of gestation were calculated. Additionally, the results of the evaluation of preventive interventions for preterm birth in these women are described.
RESULTS
In total, 34 studies were included, 24 reporting on preterm birth and 9 on preventive interventions. The pooled proportions were 46% (95% CI [39 - 53%]), 17% (95% CI [11 - 25%]), 10% (95% CI [7 - 13%]) and 2% (95% CI [1 - 3%]), regarding preterm birth <37, <34, <32 and <28 weeks in women with placenta previa. For low-lying placentas the risk of preterm birth was 30% (95% CI [19 - 43%]) and 1% (95% CI [0 - 6%]) before 37 and 34 weeks, respectively. Women with a placenta previa were more likely to have a preterm birth compared to women with a low-lying placenta or women without a placenta previa for all gestational ages. The studies about preventive interventions all showed potential prolongation of pregnancy with the use of intramuscular progesterone, intramuscular progesterone + cerclage or pessary.
CONCLUSIONS
Both women with a placenta previa and a low-lying placenta have an increased risk of preterm birth. This increased risk is consistent across all severities of preterm birth between 28-37 weeks of gestation. Women with placenta previa have a higher risk of preterm birth than women with a low-lying placenta have. Cervical cerclage, pessary and intramuscular progesterone all might have benefit for both women with placenta previa and low-lying placenta, but data in this population are lacking and inconsistent, so that solid conclusions about their effectiveness cannot be drawn.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42019123675.
Topics: Cervix Uteri; Female; Humans; Infant, Newborn; Placenta; Placenta Previa; Pregnancy; Premature Birth; Progesterone
PubMed: 36120450
DOI: 10.3389/fendo.2022.921220 -
Acta Obstetricia Et Gynecologica... Aug 2019Progestins are used as conservative treatment of endometrial hyperplasia (EH) and early endometrial cancer (EEC). We aimed to assess whether immunohistochemical... (Meta-Analysis)
Meta-Analysis
Should progesterone and estrogen receptors be assessed for predicting the response to conservative treatment of endometrial hyperplasia and cancer? A systematic review and meta-analysis.
INTRODUCTION
Progestins are used as conservative treatment of endometrial hyperplasia (EH) and early endometrial cancer (EEC). We aimed to assess whether immunohistochemical expression of estrogens and progesterone receptors (ER and PR) predicts the treatment response.
MATERIAL AND METHODS
Electronic databases were searched for studies assessing ER and PR expression in EH and EEC treated with progestins. Relative risk for poor response, sensitivity, specificity, diagnostic odds ratio positive and negative likelihood ratios (LR and LR ) and area under the curve (AUC) on summary receiver operating characteristic curve were calculated. Subgroup analyses were based on administration route (oral progestin or levonorgestrel-intrauterine device) and on histological diagnosis (atypical EH/EEC or non-atypical EH). Only high accuracy (AUC > 0.9; LR >10; LR <0.1) was considered determining for the clinical practice.
RESULTS
Thirteen studies with 635 patients were included in the systematic review. Studies at high risk of bias were excluded from the meta-analysis. Negative ER expression did not significantly predict poor response (P = 0.16), with low predictive accuracy (AUC = 0.637). Negative PR significantly predicted poor response (P = 0.01), with moderate accuracy (AUC = .806). In the oral progestin subgroup, neither ER (P = 0.55) nor PR (P = 0.18) had significant predictive value. In the levonorgestrel-intrauterine device subgroup, both ER (P < 0.0001) and PR (P = 0.02) were significantly predictive of good response, although the accuracy was suboptimal (LR 6.02 and 2.48, respectively; LR 0.59 and 0.55, respectively). The atypical EH/EEC subgroup showed non-significant results. Data about non-atypical EH were not extractable.
CONCLUSIONS
ER and PR expressions are significantly predictive of response in EH and EEC treated with a levonorgestrel-intrauterine device but not with oral progestins. However, their accuracy is insufficient to be determining in the clinical practice.
Topics: Administration, Oral; Conservative Treatment; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Intrauterine Devices, Medicated; Levonorgestrel; Progestins; Receptors, Estrogen; Receptors, Progesterone
PubMed: 30779338
DOI: 10.1111/aogs.13586