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In this trial comparing oral ulipristal acetate (5 mg or 10 mg daily) with once-monthly leuprolide acetate in women with symptomatic uterine fibroids before planned surgery, both doses of ulipristal acetate were noninferior to leuprolide acetate in controlling uterine bleeding. Uterine leiomyomas, or fibroids, are the most common benign uterine tumors in women of reproductive age. In addition to anemia caused by heavy bleeding, fibroids can cause pelvic pain, pressure, dysmenorrhea, reduced quality of life, and infertility. Current management strategies consist mainly of surgical or radiologic interventions; options for medical therapy are limited. 1 – 4 The use of oral progestin has not been extensively investigated, but small studies report breakthrough bleeding 5 and possible promotion of myoma growth. 6 The use of a progestin-releasing intrauterine device controls menorrhagia in some patients, but trials have generally excluded patients with uteri distorted by submucosal myomas. . . .

This study aimed to investigate the effects of estrogen in combination with aspirin and intrauterine balloon on the uterine endometrial repair and reproductive prognosis in patients after surgery for severe intrauterine adhesion (sIUA). We prospectively recruited 114 patients with sIUA. Intrauterine device (IUD) was placed and oral estrogen was administered after surgery. Patients were divided into control group and aspirin group. In addition, patients in aspirin group were subdivided into nonballoon group and balloon group. Results showed that, after therapy, the increase in endometrial thickness of aspirin groups was superior to control group (P<0.05). The scores of intrauterine adhesion and menstruation were significantly improved in balloon group as compared to nonballoon group and control group, and significant differences were also observed between nonballoon group and control group (P<0.05). Of 97 patients, 44.3% became pregnant after surgery, the live birth rate was 27.8%, and the miscarriage rate was 37.2%, but there were no significant differences among three groups (P>0.05). Thus, aspirin may promote the uterine endometrial growth and repair after surgery for sIUA, and IUD in combination with intrauterine balloon may reduce the recurrence of intrauterine adhesion, but their effect on the reproductive prognosis is required to be further studied.

The aim of this study was to evaluate the efficacy of hysteroscopically controlled injections of autologous platelet-rich plasma (PRP) and autologous endometrial cells as a treatment for infertile women with thin endometrium. The study enrolled 115 patients with thin endometrium (< 7 mm at implantation window) and infertility, who were divided into groups: Group 1 (the control) underwent conservative therapy; Group 2 received intraendometrial PRP injections instead of the conservative therapy; Group 3 received identical injections after conservative therapy; Group 4 received injections of the autologous endometrial cells suspended in PRP. A single injection dose of PRP contained 0.6–0.7 × 10 11 of platelets. The levels of PDGF-BB and VEGF in PRP were increased compared with ordinary plasma. The autologous endometrial cells, obtained from pipelle biopsies, constituted heterogeneous cell populations containing stromal and epithelial cells. Intraendometrial PRP injections had significant impact on endometrial thickness and local microcirculation in Group 2 and Group 3. In Group 4, injections of PRP reinforced with endometrial cells also facilitated a significant increase in endometrial thickness. This work describes a novel approach for infertility treatment in patients with refractory thin endometrium. PRP injections and injections of the endometrial cells suspended in PRP into endometrium enhanced cell proliferation and angiogenesis.

IntroductionThin endometrium poses a major therapeutic challenge in assisted reproductive technologies by compromising pregnancy success and live birth outcomes. A substantial proportion of patients remain refractory to existing therapies. Preliminary evidence suggests acupuncture may improve endometrial thickness (EMT). This study aims to assess the effect of acupuncture against sham acupuncture for women with thin endometrium.Methods and analysisThis study is a single-centre, randomised, sham-controlled trial conducted at a specialised acupuncture hospital in Beijing, China. A total of 120 women with thin endometrium will be randomised (1:1) to receive 36 sessions of acupuncture or sham acupuncture over 12 weeks. The primary outcome is the EMT at week 12. Secondary outcomes are endometrial pattern, uterine arterial blood flow parameters (Pulsatility Index, Resistance Index and the ratio of peak systolic to end-diastolic blood flow velocities), endometrium blood flow, serum oestradiol concentration, clinical pregnancy rate and Self-Rating Anxiety Scale Scores.Ethics and disseminationThis study has been approved by the ethics committee of the Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences (approval no.: S2024-04-23-1). Each participant will be required to provide written informed consent before enrolment. Findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberITMCTR2024000053.

To assess long term safety of extended repeated 3-month courses of ulipristal acetate (UPA) 10 mg/day, for up to 8 courses, with focus on endometrial and laboratory safety parameters. This long-term, multi-center, open-label cohort, follow up study consisted of up to 8 consecutive 3-month courses of daily UPA 10 mg, each separated by a drug free period of 2 spontaneous menstrual bleeds. Sixty-four pre-menopausal women, with moderate to severe symptomatic uterine myoma(s) and heavy bleeding were enrolled and were studied for approximately 4 years. The main outcome measures were endometrial histology, laboratory parameters and general safety. All data was reported in a descriptive manner with no formal statistical comparisons. In the 64 women, non-physiological changes (mostly cyst formation, epithelial and vascular changes) in endometrial histology at screening and after treatment courses 4 and 8 were observed in 18.0%, 21.4% and 16.3% of biopsies, respectively. After treatment cessation, such changes were observed in 9.1% of biopsies. All endometrial biopsies were benign after course 8. The median endometrial thickness was 7.0 mm, 10-18 days after the start of menses following treatment courses 5-8, compared to 9.0 mm at screening (before UPA treatment). No changes in the number and type of laboratory results outside the normal ranges were observed with the increasing treatment courses. In total, adverse events were reported in 10 (16%), 12 (19%), 8 (14%) and 5 (9%) subjects, during treatment courses 5, 6, 7 and 8, respectively of which the most frequent adverse events were headache and hot flush. The results of this study further support the safety profile of extended repeated 3 months treatment of symptomatic fibroids with ulipristal acetate 10 mg/day. Repeated UPA treatment courses did not result in any changes of concern in endometrial histology, endometrial thickness, or laboratory safety measures.

Background The purpose of this study was to investigate the effects of subendometrial PRP injection on endometrial thickness and pregnancy outcomes in patients with a history of unresponsive thin endometrium undergoing frozen-thawed embryo transfer (FET). Methods This prospective cohort study was conducted at Acibadem Mehmet Ali Aydinlar University-Istanbul, Turkey. Women with a history of suboptimal endometrial proliferation (< 7 mm) were offered to participate in the study. Group 1 consisted of 100 individuals who consented to subendometrial PRP injection, while Group 2 consisted of 100 individuals who did not accept PRP injection. Within ten days of the menstrual cycle ending, autologous PRP was produced by centrifuging peripheral blood and administered transvaginally into the subendometrial region under ultrasound monitoring. After the PRP procedure, 14 days of oral estradiol supplementation were started as part of the hormonal treatment on the 2-4th day of the second menstrual cycle. Women determined to have adequate endometrial thickness following the initiation were scheduled for embryo transfers. Embryo transfer was scheduled for women who were found to have adequate endometrial thickness after the initiation of progesterone. Pregnancy (positive serum hCG) and livebirth rates were followed. Results A total of 200 women (age 36.4 ± 5.8) were included in the study. Endometrial thickness increased after PRP therapy as compared to the control group (7.7 ± 1.9 mm vs. 6.1 ± 1.2 mm; p  < 0.01). Three women (3.0%) in the PRP group conceived spontaneously, whereas 97 women (97.0%) attempted FET; no spontaneous pregnancies occurred in the control group. Compared to 75/100 (75% of the total) in the control group, 33/97 women (34.0%) in the PRP group were unable to undertake ET because of persistently unresponsive thin endometrium or fluid in the endometrial cavity ( p  < 0.001). The PRP group had a considerably higher percentage of positive serum hCG tests than the control group (25.8% vs. 9.0%; p  = 0.002). Additionally, the PRP group had a higher clinical pregnancy rate (22.7% vs. 7.0%; p  = 0.002). The live birth rate was significantly higher in the PRP group than the controls (17.5% vs. 2.0%; p  < 0.001). Conclusions In women with a history of suboptimal endometrial development, subendometrial PRP injection was associated with improved endometrial thickness and livebirth rate. Trial registration Baskent University institutional review board and ethics committee (KA-20/23) http://www.Clinicaltrials.gov , (NCT04424160), 2020.06.15.

Unexplained euploid embryo transfer failure (UEETF) is a frustrating and unanswered conundrum accounting for 30 to 50% of failures in in vitro fertilization using preimplantation genetic testing for aneuploidy (PGT-A). Endometriosis is thought by many to account for most of such losses and menstrual suppression or surgery prior to the next transfer has been reported to be beneficial. In this study, we performed endometrial biopsy in a subset of women with UEETF, testing for the oncogene BCL6 and the histone deacetylase SIRT1. We compared 205 PGT-A cycles outcomes and provide those results following treatment with GnRH agonist versus controls (no treatment). Based on these and previous promising results, we next performed a pilot randomized controlled trial comparing the orally active GnRH antagonist, elagolix, to oral contraceptive pill (OCP) suppression for 2 months before the next euploid embryo transfer, and monitored inflammation and miRNA expression in blood, before and after treatment. These studies support a role for endometriosis in UEETF and suggest that medical suppression of suspected disease with GnRH antagonist prior to the next transfer could improve success rates and address underlying inflammatory and epigenetic changes associated with UEETF.

Hormonal contraception (HC) is a well-recognized protection against endometrial cancer (EC) in the general population. It has not been established if this is also applicable to women with Lynch syndrome (LS), a condition associated with a up to 50% lifetime risk of developing EC. The objective of this study was to evaluate if the use of HC influences the incidence of endometrial hyperplasia and EC in women with LS by comparing the histology of annual endometrial biopsies obtained in patients with LS who are using HC versus non-users. This is a retrospective cohort study conducted with endometrial biopsies obtained in women 30 to 50 years of age with LS. The Pearson Chi-square test was performed to compare the prevalence of cancer and hyperplasia in the HC users and in the non-HC users groups. A total of 164 endometrial biopsies obtained among 75 women were suitable for analysis. Among the 86 biopsies obtained in the non-HC group, 81.4% (70/86) were normal. Two cases of endometrial carcinoma (2.3%) and 6 endometrial hyperplasia without atypia were found (7.0%). Among the 78 biopsies performed in patients using HC, 78.2% (61/78) were normal. Three endometrial hyperplasia without atypia (3.8%) and three cases of EC were diagnosed (3.8%). This study suggests that, in women of 30 to 50 years of age with LS, the use of hormonal contraception does not seem to decrease the occurrence of endometrial hyperplasia/carcinoma on annual endometrial histology.

Background Mechanical endometrial injury prior to IVF has been suggested as a means to increase implantation rates by improving endometrial receptivity. However, the effects of endometrial injury in proliferative vs. luteal phase have not been studied before. This study aimed to explore whether endometrial injury in the proliferative phase of the preceding cycle before in vitro fertilization/embryo transfer (IVF-ET) improves the clinical outcomes in unselected subfertile women compared with injury in luteal phase. Methods A group of 142 patients who were good responders to hormonal stimulation were randomized into four groups: injury group (group A: endometrial injury in proliferative phase, n  = 38; group B: endometrium injury in luteal phase, n  = 32), and non-injury group as control (group C: non-injury in proliferative phase, n  = 36; group D: non-injury in luteal phase, n  = 36). Patients in injury groups underwent endometrial injury in either proliferative phase or luteal phase in the preceding cycle before IVF treatment. Clinical outcomes including implantation, pregnancy, and live birth rates were analyzed among the four groups. Results The baseline characteristics of the four groups including age, body mass index, duration, type and causes of infertility were similar. There were no significant differences in implantation, clinical pregnancy or live birth rates between injury group and non-injury group. Moreover, there were also no significant differences in implantation, clinical pregnancy, or live birth rates in injury in proliferative phase compared with luteal phase. Conclusions Endometrial injury in the cycle preceding IVF of unselected subfertile women does not increase implantation, clinical pregnancy, or live birth rates. Furthermore, there is no significant difference in clinical outcomes between endometrial injury in the proliferative phase and injury in the luteal phase. Trial registration This study was retrospectively registered on May 26th, 2017 (ChiCTR-IOR-17011506).

ObjectiveGonadotropin-releasing hormone agonists (GnRHa), combined with other auxiliary treatments, can improve pregnancy outcomes in in vitro fertilization-embryo transfer (IVF-ET). This research investigated the effect of acupuncture combined with GnRHa in patients with recurrent implantation failure (RIF) of IVF-ET.MethodsA total of 164 patients who intended to undergo frozen-thawed embryo transfer after RIF of IVF-ET were selected for experiments and then divided into the control (received conventional hormone replacement therapy (HRT) for endometrial preparation) and study groups (received a combination of acupuncture, GnRHa, and HRT for endometrial preparation) (n = 82). Endometrial thickness (EMT), endometrial morphological classification, submucosal uterine blood flow classification, clinical pregnancy rate, embryo implantation rate, and early abortion rate for each transfer cycle were compared between the two groups.ResultsEMT of the study group was higher than that of the control group 1 day before transfer. There were more patients with linear endometrium (A + B type) in the study group on the day of endometrial transformation than in the control group. The number of patients with type I submucosal uterine blood flow in the study group was decreased and the number of patients with type III was increased compared with the control group on the day of endometrial transformation. The clinical pregnancy rate and embryo implantation rate of the study group were higher than those of the control group.ConclusionAcupuncture combined with GnRHa improves the endometrial receptivity of patients with RIF of IVF-ET, thereby increasing clinical pregnancy rates and improving pregnancy outcomes.