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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 -
Frontiers in Cellular and Infection... 2021Exogenous sex steroids within hormonal contraception and menopausal hormone therapy (MHT) have been used for family planning and management of menopausal symptoms,...
BACKGROUND
Exogenous sex steroids within hormonal contraception and menopausal hormone therapy (MHT) have been used for family planning and management of menopausal symptoms, without consideration of their effects on the vaginal microbiota. This is largely because their use predates our understanding of the importance of the vaginal microbiome on human health. We conducted a systematic review (PROSPERO: CRD42018107730) to determine the influence of exogenous sex steroids, stratified by oestrogen-containing or progestin-only types of contraception, and MHT on the vaginal microbiome, as measured by molecular methods.
METHODS
Embase, PubMed and Medline were searched for relevant literature published through to December 1st 2020. Eligible studies reported on the effect of specific exogenous sex steroids on the vaginal microbiome using a molecular method. Data regarding the 'positive', 'negative' or 'neutral' effect of each type of contraceptive or MHT on the vaginal microbiome was extracted and summarised. A positive effect reflected sex steroid exposure that was associated with increased abundance of lactobacilli, a change to, or maintenance of, an optimal vaginal microbiota composition, or a decrease in bacterial diversity (specifically reflecting a low-diversity optimal microbiota state), relative to the control group. An exogenous sex steroid was designated as having a negative effect on the vaginal microbiome if it resulted in opposing effects (i.e. loss of lactobacilli, a non-optimal microbiota state). When no significant change was found, this was considered neutral/inconclusive.
RESULTS
We identified 29 manuscripts reporting on the effect of exogenous sex steroids on the vaginal microbiome; 25 investigating hormonal contraceptives, and 4 investigating MHT. Oestrogen-containing contraception, particularly reflecting the combined oestrogen and progestin-containing contraceptive pill, had a positive effect on the composition of the vaginal microbiota. Progestin-only contraception, particularly reflecting depo-medroxyprogesterone acetate, had mixed effects on the microbiota. Among post-menopausal women using MHT, exogenous oestrogen applied topically was associated with increased prevalence of lactobacilli.
CONCLUSION
Our findings suggest that oestrogen-containing compounds may promote an optimal vaginal microbiota, which could have clinical applications. The impact of progestin-only contraceptives on the vaginal microbiota is less clear; more data is needed to determine how progestin-only contraceptives contribute to adverse reproductive and sexual health outcomes.
Topics: Female; Humans; Lactobacillus; Microbiota; Vagina
PubMed: 34869054
DOI: 10.3389/fcimb.2021.732423 -
Annals of Palliative Medicine Oct 2021This study aimed to explore the clinical efficacy of dydrogesterone in treating recurrent spontaneous abortion (RSA), analyze the influence of dydrogesterone on cellular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study aimed to explore the clinical efficacy of dydrogesterone in treating recurrent spontaneous abortion (RSA), analyze the influence of dydrogesterone on cellular immune factors, and provide evidence for clinical medication.
METHODS
We used the China National Knowledge Infrastructure (CNKI) platform, Wanfang Data resource, PubMed, Web of Science, and Embase database to conduct a literature search to screen clinical studies published between 2005 and 2021 concerning dydrogesterone treatment for RSA. Stata 16.0 was used for meta-analysis and sensitivity analysis, and Begg's funnel chart was used to test publication bias.
RESULTS
Only 13 studies, which included a total of 2,454 RSA patients, met the study inclusion criteria. The experimental group was treated with dydrogesterone, and the control group was treated with progesterone, human chorionic gonadotropin (hCG), placebo, or active immunization. Meta-analysis showed that the pregnancy success rate of the experimental group was higher than the control group, and the adverse reaction rate was lower than the control group. In addition, subgroup analysis also revealed that the experimental group had a higher pregnancy success rate than the control group and a lower adverse reaction rate. Levels of progesterone and hCG in the experimental group were dramatically higher than the control group after treatment. The experimental group also had higher levels of interleukin 4 (IL-4) and interleukin 10 (IL-10) than the control group, while levels of interferon-gamma (IFN-γ) were lower.
DISCUSSION
Dydrogesterone, a safe and effective synthetic progesterone drug, had a significant clinical effect on RSA and effectively improved hormone levels and related cellular immune factors in RSA patients.
Topics: Abortion, Habitual; China; Dydrogesterone; Female; Humans; Immunologic Factors; Pregnancy; Progesterone
PubMed: 34763460
DOI: 10.21037/apm-21-2605 -
Contraception Mar 2022Studies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the...
OBJECTIVE
Studies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the effects of other forms of hormonal contraception (HC). We examine whether HC use increases the risk of incident cervical intraepithelial neoplasia (CIN) 2, 3 and/or cancer after accounting for preexisting human papillomavirus (HPV) infection.
STUDY DESIGN
Systematic review of prospective studies on HC use as risk factor for cervical dysplasia with HPV infection documented prior to outcome assessment including PubMed and EMBASE records between January 2000 and February 2020 (Prospero #CRD42019130725).
RESULTS
Among nine eligible studies, seven described recency and type of HC use and therefore comprise the primary analysis; two studies limit comparisons to ever versus never use and are summarized separately. All seven studies explored the relationship between oral contraceptive (OC) use and cervical dysplasia/cancer incidence: two found increased risk (adjusted odds ratio, aOR = 1.5-2.7), one found no association but decreased risk when restricted to women with persistent HPV (adjusted hazard ratio = 0.5), and four found no association. None of the seven studies differentiated between COC and progestin-only pills (POPs) by use recency or duration. The only study that included injectable progestin-only contraception (DMPA) found increased CIN3 incidence among current versus never users (aOR = 1.6). The one study that included Norplant found no association. Two studies included intrauterine device (IUD) use, but did not differentiate between hormonal and copper IUDs, and found no association.
CONCLUSION
We found no consistent evidence that OC use is associated with increased risk for cervical dysplasia/cancer after controlling for HPV infection. There were too few studies of progestin-only injectables, implants or IUDs to assess their effect on cervical dysplasia/cancer risk.
IMPLICATIONS
Use of single self-reported HC measures and insufficient distinction by hormonal constituent cloud our understanding of whether some HCs increase risk for cervical cancer. Methodologically rigorous studies with distinct HCs measured as time-varying exposures are needed to inform cervical cancer prevention efforts and improve our understanding of cervical cancer etiology.
Topics: Contraceptives, Oral, Hormonal; Female; Hormonal Contraception; Humans; Papillomavirus Infections; Progestins; Prospective Studies; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 34752778
DOI: 10.1016/j.contraception.2021.10.018 -
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 -
PloS One 2021The long-term use of contraceptive methods that contain estrogens, progestogens or combinations of the above among women aged 15 to 49 years is extensive. Both estrogens...
BACKGROUND
The long-term use of contraceptive methods that contain estrogens, progestogens or combinations of the above among women aged 15 to 49 years is extensive. Both estrogens and progestogens affect bone metabolism.
OBJECTIVE
To systematically investigate and appraise the quality of the available evidence from animal studies regarding the impact of exogenous administration of female sex hormones on the rate of orthodontic tooth movement and root resorption.
SEARCH METHODS
Search without restriction in seven databases (including grey literature) and hand searching were performed until May 2021.
SELECTION CRITERIA
We looked for controlled animal studies investigating the effect from exogenous administration of formulations containing female sex hormones on the rate of orthodontic tooth movement and root resorption.
DATA COLLECTION AND ANALYSIS
After study retrieval and selection, relevant data was extracted, and the risk of bias was assessed using the SYRCLE's Risk of Bias Tool. The quality of available evidence was assessed with the Grades of Recommendation, Assessment, Development, and Evaluation.
RESULTS
Three studies were identified, all being at unclear risk of bias. Overall, administration of progesterone and the combinations of estradiol with norgestrel and desogestrel were shown to significantly decrease the rate of orthodontic tooth movement when given for longer periods (>3 weeks). Inconsistent information was detected for shorter periods of consumption. Estradiol, with desogestrel use, resulted in less root resorption. The quality of the available evidence was considered to be low.
CONCLUSIONS
Exogenous administration of female sex hormones may decelerate in the long term the rate of tooth movement and decrease orthodontically induced root resorption in animals. Until more information becomes available, an orthodontist should be able to identify a patient consuming such substances and understand the potential clinical implications and adverse effects that may arise.
REGISTRATION
PROSPERO: CRD42017078208; https://clinicaltrials.gov/.
Topics: Adolescent; Adult; Animals; Animals, Laboratory; Contraceptives, Oral, Hormonal; Disease Models, Animal; Female; Gonadal Steroid Hormones; Humans; Middle Aged; Progestins; Root Resorption; Time Factors; Tooth Mobility; Young Adult
PubMed: 34582488
DOI: 10.1371/journal.pone.0257778 -
Frontiers in Endocrinology 2021Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that can block the luteinizing hormone (LH) surge through progesterone instead of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that can block the luteinizing hormone (LH) surge through progesterone instead of traditional down regulating or gonadotropin-releasing hormone (GnRH) antagonist, and in order to achieve multi-follicle recruitment. This paper aims to investigate the effectiveness of PPOS and its suitability for infertile patients with different ovarian reserve functions.
METHODS
We searched published randomized controlled trials (RCTs) about PPOS on Cochrane Library, PubMed, Embase, and Web of Science. The search period spanned from January 1, 2015 to November 16, 2020. The data were extracted, and the meta-analysis was performed on ovarian stimulation as well as embryological and clinical outcomes. The outcomes were pooled by a random effects model, and the risk of heterogeneity was evaluated. Subgroup analysis was performed for different ovarian reserve patients.
RESULTS
The clinical pregnancy rates and live birth or ongoing pregnancy rates with the PPOS protocol were not different from those with the control group. In the diminished ovarian reserve (DOR) subgroup, the PPOS protocol had a lower rate of premature LH surge [RR = 0.03, 95% CI = 0.01 to 0.13, < 0.001]. The PPOS protocol had a lower rate of ovarian hyperstimulation syndrome (OHSS) [RR = 0.52, 95% CI = 0.36 to 0.76, < 0.001, = 0.00%]. The secondary outcomes showed that the number of oocytes retrieved, MII oocytes, and viable embryos was higher than that of the control protocol in DOR patients [(MD = 0.33, 95% CI = 0.30 to 0.36, < 0.001), (MD = 0.30, 95% CI = 0.27 to 0.33, < 0.001), (MD = 0.21, 95% CI = 0.18 to 0.24, < 0.001)] and normal ovarian reserve (NOR) patients [(MD = 1.41, 95% CI = 0.03 to 2.78, < 0.001), (MD = 1.19, 95% CI = 0.04 to 2.35, < 0.001), (MD = 1.01, 95% CI = 0.21 to 1.81, = 0.01)].
CONCLUSION
The findings suggest that PPOS is an effective ovarian stimulation protocol and is beneficial for patients with different ovarian reserve functions, which needs to be validated in more RCTs with larger samples.
Topics: Female; Humans; Pregnancy; Fertilization in Vitro; Infertility, Female; Live Birth; Ovarian Reserve; Ovulation Induction; Pregnancy Rate; Progestins; Randomized Controlled Trials as Topic
PubMed: 34531825
DOI: 10.3389/fendo.2021.702558 -
Fertility and Sterility Dec 2021To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Women undergoing FET.
INTERVENTION(S)
We conducted electronic searches of MEDLINE, PubMed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and grey literature (not widely available) from inception to March 2021 to identify cohort studies in which the serum luteal progesterone level was measured around the time of FET.
MAIN OUTCOME MEASURE(S)
Ongoing pregnancy or live birth rate, clinical pregnancy rate, and miscarriage rate.
RESULT(S)
Among the studies analyzing serum progesterone level thresholds <10 ng/mL, a higher serum progesterone level was associated with increased rates of ongoing pregnancy or live birth (relative risk [RR] 1.47, 95% confidence interval [CI] 1.28 to 1.70), higher chance of clinical pregnancy (RR 1.31, 95% CI 1.16 to 1.49), and lower risk of miscarriage (RR 0.62, 95% CI 0.50 to 0.77) in cycles using exclusively vaginal progesterone and blastocyst embryos. There was uncertainty about whether progesterone thresholds ≥10 ng/mL were associated with FET outcomes in sensitivity analyses including all studies, owing to high interstudy heterogeneity and wide CIs.
CONCLUSION(S)
Our findings indicate that there may be a minimum clinically important luteal serum concentration of progesterone required to ensure an optimal endocrine milieu during embryo implantation and early pregnancy after FET treatment. Future clinical trials are required to assess whether administering higher-dose luteal phase support improves outcomes in women with a low serum progesterone level at the time of FET.
PROSPERO NUMBER
CRD42019157071.
Topics: Cryopreservation; Embryo Transfer; Female; Humans; Live Birth; Luteal Phase; Pregnancy; Pregnancy Rate; Progesterone; Prospective Studies; Reproductive Techniques, Assisted; Retrospective Studies
PubMed: 34384594
DOI: 10.1016/j.fertnstert.2021.07.002 -
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 -
Pharmaceuticals (Basel, Switzerland) Jun 2021Progestin-only contraceptive implants provide long-acting, highly effective reversible contraception. We searched the medical publications in PubMed, CENTRAL, and EMBASE... (Review)
Review
Progestin-only contraceptive implants provide long-acting, highly effective reversible contraception. We searched the medical publications in PubMed, CENTRAL, and EMBASE for relevant articles on hormonal implants published in English between 1990 and 2021. Levonorgestrel (LNG) 6-capsule subdermal implants represented the first effective system approved for reversible contraception. The etonogestrel (ENG) single rod dispositive has been widely employed in clinical practice, since it is a highly effective and safe contraceptive method. Abnormal menstrual bleeding is a common ENG side effect, representing the main reason for its premature discontinuation. Emerging evidence demonstrated that it is possible to extend the use of the ENG implant beyond the three-year period for which it is approved. The ENG implant could be an effective and discrete alternative to the IUD in young girls, such as post-partum/post-abortion. Implants should be inserted by trained skilled clinicians who previously provide adequate counselling about their contraceptive effect, benefits, and any possible adverse events. More studies are needed to validate the extended use of the ENG implant for up to 5 years.
PubMed: 34201123
DOI: 10.3390/ph14060548