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Background Progestins can block endogenous luteinizing hormone secretion from the pituitary gland and have shown similar efficacy in terms of collecting competent oocytes and embryos; however, some inconsistencies have been proposed by the previous papers regarding the quality of oocytes and embryos obtained with the use of progestins. This study aimed to compare the euploidy rate between women treated with progestin-primed ovarian stimulation (PPOS) and the gonadotropin-releasing hormone (GnRH) antagonist protocol. Methods This is a prospective randomized study of 240 infertile women undergoing PGT-A between August 2021 and July 2023. Infertile women with advanced maternal age (38–45 years), recurrent pregnancy loss (≥ 2 or 3 consecutive miscarriages), and repeated implantation failure (≥ 4 embryos replaced or ≥ 2 blastocysts replaced without success) undergoing PGT-A cycles were included. Women were randomly assigned into the PPOS group ( n  = 120) or the antagonist group ( n  = 120) according to a computer-generated randomization list. Dydrogesterone 20 mg per day was given from the start of ovarian stimulation until the trigger day in the PPOS group. In the antagonist group, an antagonist 0.25 mg was given daily from the sixth day of ovarian stimulation until the trigger day. The primary outcome measure was the euploidy rate, defined as the number of euploid blastocysts per injected oocyte. Results No significant differences were observed in the demographic and ovarian stimulation characteristics between the two groups. The euploidy rate was comparable between the PPOS and antagonist group (12.5% vs. 16.0% respectively, P  > 0.05). No significant differences were observed between the two groups in positive pregnancy test, clinical pregnancy, miscarriage, ectopic pregnancy, or live birth rates per transfer in the first frozen embryo transfer cycles. Conclusion Both PPOS and antagonist protocols had similar euploidy rates in PGT-A cycles. Trial registration Clinicaltrials. gov identifier: NCT04989348 ( https://www.clinicaltrials.gov/ ). Trial registration date: Clinicaltrials. gov: 30 July 2021.

AbstractObjectivesTo evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain.DesignThe PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel group, open label, randomised controlled trial.Setting34 UK hospitals.Participants405 women of reproductive age undergoing conservative surgery for endometriosis.InterventionsParticipants were randomised in a 1:1 ratio using a secure internet facility to a long acting progestogen (depot medroxyprogesterone acetate or levonorgestrel releasing intrauterine system) or the combined oral contraceptive pill.Main outcome measuresThe primary outcome was pain measured three years after randomisation using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at six months, one, two, and three years) included the four core and six modular domains of the EHP-30, and treatment failure (further therapeutic surgery or second line medical treatment).Results405 women were randomised to receive a long acting progestogen (n=205) or combined oral contraceptive pill (n=200). At three years, there was no difference in pain scores between the groups (adjusted mean difference −0.8, 95% confidence interval −5.7 to 4.2, P=0.76), which had improved by around 40% in both groups compared with preoperative values (an average of 24 and 23 points for long acting progestogen and combined oral contraceptive pill groups, respectively). Most of the other domains of the EHP-30 also showed improvement at all time points compared with preoperative scores, without evidence of any differences between groups. Women randomised to a long acting progestogen underwent fewer surgical procedures or second line treatments compared with those randomised to the combined oral contraceptive pill group (73 v 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00).ConclusionsPostoperative prescription of a long acting progestogen or the combined oral contraceptive pill results in similar levels of improvement in endometriosis related pain at three years, with both groups showing around a 40% improvement compared with preoperative levels. While women can be reassured that both options are effective, the reduced risk of repeat surgery for endometriosis and hysterectomy might make long acting reversible progestogens preferable for some.Trial registrationISRCTN registry ISRCTN97865475.

ObjectivesTo evaluate the cost-effectiveness of long-acting progestogens (LAP), including levonorgestrel-releasing intrauterine system (LNG-IUS) and depot-medroxyprogesterone acetate (DMPA), compared with the combined oral contraceptives pill (COCP) in preventing recurrence of endometriosis-related pain postsurgery.DesignWithin-trial economic evaluation alongside a multicentre, pragmatic, parallel-group, open-label, randomised controlled trial (Preventing Recurrence of Endometriosis by means of Long-Acting Progestogen Therapy trial).SettingThirty-four UK hospitals recruiting participants from November 2015 to March 2019.PatientsFour hundred and five women aged 16–45 years undergoing conservative endometriosis surgery.InterventionsThe ratio of 1:1 randomisation to receive LAPs (LNG-IUS or DMPA) or COCP.Main outcome measuresThe primary evaluation was a cost-utility analysis based on cost per quality-adjusted life-year (QALY) gained at 3 years. We adopted a UK National Health Service perspective. Secondary analyses in the form of cost-effectiveness analysis based on a range of outcomes were also undertaken.ResultsFor the primary analysis, the COCP group incurred an additional cost of £533 (95% CI £52 to £983) per woman compared with LAPs. Treatment with COCP generated additional QALYs of 0.031 (95% CI −0.079 to 0.139) compared with the LAP group over 36-month follow-up. The incremental cost-effectiveness ratio for COCP compared with LAPs is therefore approximately £17 193 per QALY. The probabilistic sensitivity analysis suggested that there was a 54.7% probability that COCP would be cost-effective at the £20 000/QALY threshold. The secondary analyses revealed results more in favour of LAPs.ConclusionAlthough the COCP has a slightly higher probability of being cost-effective at £20 000/QALY threshold, there remains considerable uncertainty, with only marginal differences in outcomes between the two treatments. The lower rates of further surgery and second-line medical treatment for women allocated to LAPs may make this option preferable for some women.Trial registration numberISRCTN 97865475.

Background The use of progestin (P) during ovarian stimulation is effective in blocking the luteinizing hormone (LH) surge in women with normal ovarian reserve, however, its effects have not been determined in poor responders. This study aimed to explore the follicular dynamics in P-primed minimal stimulation in poor responders. Methods A total of 204 infertile women with diminished ovarian reserve were allocated into the medroxyprogesterone acetate (MPA) group or the natural-cycle control group in an alternating order. MPA (10 mg) was administered daily beginning from the early follicular phase and a low dose of hMG was added in the late follicular phase if the serum FSH level was lower than 8.0mIU/ml. When a dominant follicle reached maturity, triptorelin 100 μg and hCG 1000 IU were used for trigger, and oocytes were retrieved 34-36 h later.All viable embryos were cryopreserved for subsequent frozen embryo transfer. Natural cycle IVF was used as controls. Results Compared with the natural cycle group, the MPA group exhibited a larger pre-ovulatory follicle (18.7 ± 1.8 mm vs 17.2 ± 2.2 mm), a longer follicular phase (13.6 ± 3.6 days vs 12.3 ± 3.2 days), and higher peak oestradiol values (403.88 ± 167.16 vs 265.26 ± 122.16 pg/ml), while maintaining lower LH values ( P  < 0.05). The incidences of spontaneous LH surge and premature ovulation decreased significantly (1.0% vs 50%; 2% vs. 10.8%, respectively; P  < 0.05). A greater number of oocytes and viable embryos were harvested from the MPA group than from the natural cycle group ( P  < 0.05). Moreover,the clinical pregnancy rate was slightly higher in the MPA group than in the natural cycle controls, but the difference was not significant (11.8% vs 5.9%, P  > 0.05). Conclusion This study supported the hypothesis that P-primed minimal stimulation achieved ovulation control of the dominant follicle and did not adversely affect the quality of oocytes in poor responders. Therefore, P-priming is a promising approach to overcome premature ovulation in minimal stimulation for poor responders. Trial registration ChiCTR-OCH-14004176 . Registered on January 8, 2014.

In this multicenter, randomized, double-blind, placebo-controlled trial involving women with vaginal bleeding in early pregnancy, treatment with progesterone during the first trimester did not result in a significantly higher incidence of live births than placebo.

In this pragmatic, randomized trial of women with menorrhagia, the levonorgestrel-releasing intrauterine system was more effective than the usual (oral) medical treatment in reducing the effect of this problem on quality of life. Heavy menstrual bleeding, or menorrhagia, is a common problem that can have a significant effect on women's lives and can burden both patients and health care systems. 1 , 2 Menorrhagia accounts for 18.5% of gynecologist office visits in the United States 3 and for 20% in the United Kingdom 4 ; more than 5% of women who are 30 to 49 years of age consult family physicians each year in the United Kingdom with this problem. 5 Rates of surgical procedures for menorrhagia are 17.8 per 10,000 women 25 to 44 years of age in the United States 6 and 14.3 per 10,000 women 24 . . .

In this study, the biocatalytic activity of four steroid-transforming strains isolated from the African frog Xenopus laevis and identified as Streptomyces rochei towards pregnane steroids has been investigated. All the isolated strains facilitated the reduction of the C20-carbonyl group and the structures of the metabolites were confirmed by mass spectrometric (MS) and 1H NMR spectroscopic analyses. Hydrocortisone and progesterone were poorly transformed by the streptomycete strains, whereas cortexolone (Reichstein’s substance S) was effectively biotransformed, yielding more than 90% of 17α,20β,21α-trihydroxy-4-pregnen-3-one (20β-S). Primarily, 20α-reduction was detected when the microbial isolates were incubated with 17α-hydroxyprogesterone with the yield of 17α,20α-dihydroxy-4-pregnen-3-one (17,20α-P) reaching 70%. The biological activity of 20β-S was evaluated in Danio rerio. The results demonstrated that 20β-S modulated stress- and anxiety-related behavioral responses and activated Pgr-dependent transcriptional pathways in the brain and ovarian tissues. These observations support the potential relevance of the synthesized progestin as a functional regulator in teleost physiology. The findings enhance our understanding of the biodiversity of steroid-transforming actinomycetes inhabiting amphibians and can be successfully employed for the effective microbiological synthesis of biologically active 20-hydroxylated progestins that serve as bioregulators in teleosts.

Women with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy. In this double-blind, placebo-controlled trial, 500 women with twin pregnancy were recruited from nine UK National Health Service clinics specialising in the management of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes, either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for 10 weeks from 24 weeks' gestation. All study personnel and participants were masked to treatment assignment for the duration of the study. The primary outcome was delivery or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat. Additionally we undertook a meta-analysis of published and unpublished data to establish the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm birth or intrauterine death in women with twin pregnancy. This study is registered, number ISRCTN35782581. Three participants in each group were lost to follow-up, leaving 247 analysed per group. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was 24·7% (61/247) in the progesterone group and 19·4% (48/247) in the placebo group (odds ratio [OR] 1·36, 95% CI 0·89–2·09; p=0·16). The rate of adverse events did not differ between the two groups. The meta-analysis confirmed that progesterone does not prevent early preterm birth in women with twin pregnancy (pooled OR 1·16, 95% CI 0·89–1·51). Progesterone, administered vaginally, does not prevent preterm birth in women with twin pregnancy. Chief Scientist Office of the Scottish Government Health Directorate.

Background Preterm birth (PTB) is a costly public health problem in the USA. The PREGNANT trial tested the efficacy of vaginal progesterone (VP) 8 % gel in reducing the likelihood of PTB among women with a short cervix. Objective We calculated the costs and cost effectiveness of VP gel versus placebo using decision analytic models informed by PREGNANT patient-level data. Methods PREGNANT enrolled 459 pregnant women with a cervical length of 10–20 mm and randomized them to either VP 8 % gel or placebo. We used a cost model to estimate the total cost of treatment per mother and a cost-effectiveness model to estimate the cost per PTB averted with VP gel versus placebo. Patient-level trial data informed model inputs and included PTB rates in low- and high-risk women in each study group at <28 weeks gestation, 28–31, 32–36, and ≥37 weeks. Cost assumptions were based on 2010 US healthcare services reimbursements. The cost model was validated against patient-level data. Sensitivity analyses were used to test the robustness of the cost-effectiveness model. Results The estimated cost per mother was $US23,079 for VP gel and $US36,436 for placebo. The cost-effectiveness model showed savings of $US24,071 per PTB averted with VP gel. VP gel realized cost savings and cost effectiveness in 79 % of simulations. Conclusion Based on findings from PREGNANT, VP gel was associated with cost savings and cost effectiveness compared with placebo. Future trials designed to include cost metrics are needed to better understand the value of VP.

Progesterone administration has been shown to reduce the risk of preterm birth and neonatal morbidity in women at high risk, but there is uncertainty about longer term effects on the child. We did a double-blind, randomised, placebo-controlled trial of vaginal progesterone, 200 mg daily taken from 22–24 to 34 weeks of gestation, on pregnancy and infant outcomes in women at risk of preterm birth (because of previous spontaneous birth at ≤34 weeks and 0 days of gestation, or a cervical length ≤25 mm, or because of a positive fetal fibronectin test combined with other clinical risk factors for preterm birth [any one of a history in a previous pregnancy of preterm birth, second trimester loss, preterm premature fetal membrane rupture, or a history of a cervical procedure to treat abnormal smears]). The objective of the study was to determine whether vaginal progesterone prophylaxis given to reduce the risk of preterm birth affects neonatal and childhood outcomes. We defined three primary outcomes: fetal death or birth before 34 weeks and 0 days gestation (obstetric), a composite of death, brain injury, or bronchopulmonary dysplasia (neonatal), and a standardised cognitive score at 2 years of age (childhood), imputing values for deaths. Randomisation was done through a web portal, with participants, investigators, and others involved in giving the intervention, assessing outcomes, or analysing data masked to treatment allocation until the end of the study. Analysis was by intention to treat. This trial is registered at ISRCTN.com, number ISRCTN14568373. Between Feb 2, 2009, and April 12, 2013, we randomly assigned 1228 women to the placebo group (n=610) and the progesterone group (n=618). In the placebo group, data from 597, 587, and 439 women or babies were available for analysis of obstetric, neonatal, and childhood outcomes, respectively; in the progesterone group the corresponding numbers were 600, 589, and 430. After correction for multiple outcomes, progesterone had no significant effect on the primary obstetric outcome (odds ratio adjusted for multiple comparisons [OR] 0·86, 95% CI 0·61–1·22) or neonatal outcome (OR 0·72, 0·44–1·17), nor on the childhood outcome (cognitive score, progesterone group vs placebo group, 97·3 [SD 17·9] vs 97·7 [17·5]; difference in means –0·48, 95% CI –2·77 to 1·81). Maternal or child serious adverse events were reported in 70 (11%) of 610 patients in the placebo group and 59 (10%) of 616 patients in the progesterone group (p=0·27). Vaginal progesterone was not associated with reduced risk of preterm birth or composite neonatal adverse outcomes, and had no long-term benefit or harm on outcomes in children at 2 years of age. Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. The EME Programme is funded by the MRC and NIHR, with contributions from the Chief Scientist Office in Scotland and National Institute for Social Care and Research in Wales.