Human reproduction open最新文献

{"title":"Correction to: The interplay between mitochondrial DNA genotypes, female infertility, ovarian response, and mutagenesis in oocytes.","authors":"","doi":"10.1093/hropen/hoaf037","DOIUrl":"https://doi.org/10.1093/hropen/hoaf037","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/hropen/hoae074.].</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf037"},"PeriodicalIF":8.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12233084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endometrial compaction shows no association with improved pregnancy outcomes in hormonal replacement frozen-thawed embryo transfer: an analysis of over 16 000 cases.","authors":"Peipei Pan, Chang Liu, Shiyi Lin, Haiqing Wang, Xia Chen, Haiyan Yang, Xuefeng Huang, Huan Zhang, Yili Teng","doi":"10.1093/hropen/hoaf039","DOIUrl":"10.1093/hropen/hoaf039","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Is there an association between changes in endometrial thickness (EMT) following progesterone administration and pregnancy outcomes in frozen-thawed embryo transfers (FETs) at Day 3 (D3) and blastocyst stages?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Endometrial compaction is not associated with better pregnancy outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Previous studies have shown conflicting results on the impact of EMT changes on FET outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This study was a single-center retrospective cohort analysis of FETs from 1 January 2018 to 31 December 2022. A total of 9390 D3 FETs and 7063 blastocyst FETs were included during this period.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;D3 FETs and blastocyst FETs were divided into three groups: compaction group, non-change group, and expansion group. The impact of EMT changes after progesterone administration on HCG-positive, pregnancy, ongoing pregnancy, live birth, and pregnancy loss rates were analyzed for D3 and blastocyst FETs. EMT on the progesterone administration day (defined as EMT1) and on embryo transfer (ET)day (defined as EMT2) was measured exclusively by transvaginal ultrasound. Inverse probability weighting (IPW) and stratified logistic regressions were conducted to reduce the effects of confounding factors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;After IPW adjustment, in D3 FETs, women with compacted endometrium had the lowest HCG-positive rates (&lt;i&gt;P &lt;/i&gt;= 0.012), clinical pregnancy rates (&lt;i&gt;P &lt;/i&gt;&lt; 0.001), ongoing pregnancy rates (&lt;i&gt;P &lt;/i&gt;&lt; 0.001), and live birth rates (LBRs) (&lt;i&gt;P &lt;/i&gt;&lt; 0.001) among the three groups. Among HCG-positive cases, the compaction group had the highest ectopic pregnancy rates (3.5% vs 2.6% vs 1.6%; &lt;i&gt;P &lt;/i&gt;= 0.015) and the lowest LBRs (65.8% vs 68.3% vs 71.4%; &lt;i&gt;P &lt;/i&gt;= 0.018). Univariate logistic regressions found that LBRs were weakly associated with compacted endometrium [odds ratio (OR) 0.831, 95% CI: 0.696-0.993]. Logistic regressions with IPW revealed that the compaction group was not associated with higher odds of pregnancy outcomes, including HCG positive, clinical pregnancy, ongoing pregnancy, ongoing pregnancy, and live births compared to the non-change group. In contrast, the expansion group was associated with higher odds of live birth per ETs (OR 1.166, 95% CI: 1.070-1.271; &lt;i&gt;P &lt;/i&gt;= 0.001), and live birth per HCG-positive cases (OR 1.160, 95% CI: 1.028-1.309; &lt;i&gt;P &lt;/i&gt;= 0.016). In blastocyst FETs, women with compacted endometrium had the lowest HCG-positive rates (&lt;i&gt;P &lt;/i&gt;= 0.001) and clinical pregnancy rates (&lt;i&gt;P &lt;/i&gt;= 0.031). Logistic regressions with IPW adjustment found that compaction group was associated with lower odds of HCG positive (OR 0.813, 95% CI: 0.668-0.989, &lt;i&gt;P &lt;/i&gt;= 0.039) compared to the non-change group. Additionally, LBRs increased with the rising change ratios of EMT after progeste","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf039"},"PeriodicalIF":8.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Birth defects reporting and the use of dydrogesterone: a disproportionality analysis from the World Health Organization pharmacovigilance database (VigiBase).","authors":"","doi":"10.1093/hropen/hoaf029","DOIUrl":"https://doi.org/10.1093/hropen/hoaf029","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/hropen/hoae072.].</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf029"},"PeriodicalIF":8.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Uterine smooth muscle tumours with uncertain malignant potential: reproductive and clinical outcomes in patients undergoing fertility-sparing management.","authors":"","doi":"10.1093/hropen/hoaf032","DOIUrl":"https://doi.org/10.1093/hropen/hoaf032","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/hropen/hoaf009.].</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf032"},"PeriodicalIF":8.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why does the latest pharmacovigilance data not reflect clinical experience with dydrogesterone?","authors":"Emre Pabuccu, Angela Aguilar, Roberto de Azevedo Antunes, Eran Gefen, Lee P Shulman","doi":"10.1093/hropen/hoaf030","DOIUrl":"10.1093/hropen/hoaf030","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf030"},"PeriodicalIF":8.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Fetal safety of dydrogesterone: clarifying the role of pharmacovigilance.","authors":"Laurent Chouchana, Alexandra Henry, Mathilde Bourdon, Chloé Maignien, Charles Chapron, Jean-Marc Treluyer, Jean Guibourdenche, Pietro Santulli","doi":"10.1093/hropen/hoaf031","DOIUrl":"10.1093/hropen/hoaf031","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf031"},"PeriodicalIF":8.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressively diminished estrogen signaling concordant with increased fibrosis in ectopic endometrium.","authors":"Jichan Nie, Yunhua Yi, Xishi Liu, Sun-Wei Guo","doi":"10.1093/hropen/hoaf028","DOIUrl":"10.1093/hropen/hoaf028","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Do all ectopic endometrial lesions (endometriosis and adenomyosis) universally have activated estrogen signaling?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Estrogen signaling diminishes concordantly with increased fibrosis in ectopic endometrium, with deep endometriotic (DE) lesions exhibiting an estrogen biosynthesis capability and estrogen receptor β (ERβ) expression level comparable to that of control endometrium but having suppressed ERα.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Endometriosis and adenomyosis are both estrogen-dependent diseases driven by estrogen-mediated lesional development, progression, and symptom manifestation. Of note, ectopic endometrium is thought to have the ability to synthesize estradiol (E&lt;sub&gt;2&lt;/sub&gt;) &lt;i&gt;in situ&lt;/i&gt; from cholesterol due to upregulation of aromatase (CYP19A1), steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase type 2 (HSD3β2), and HSD17β1. In addition to increased estrogen biosynthesis, ERβ and G-protein coupled ER (GPER) are also overexpressed in ectopic endometrium. In particular, the prevailing view holds that prostaglandin E2 plays a vital role in facilitating estrogen biosynthesis and the upregulation of ERβ, positioning itself in the central nexus in a feed-forward loop linking hyperestrogenism and inflammation in all ectopic endometria.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;After obtaining written informed consent, we collected lesional tissues from 19 patients with ovarian endometriosis (OE) and 20 patients each with adenomyosis (AD) and DE. As controls, normal endometrial tissue samples (CT) were procured from 20 cycling women free of endometriosis and adenomyosis, and age- and menstrual phase-matched with patients in the other groups. Additionally, primary ectopic or control endometrial stromal cells derived from eight subjects in each of the OE, AD, DE, and CT groups were cultured for experiments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;We performed immunohistochemistry and western blotting to assess the expression of proteins key to the estrogen biosynthesis (StAR, HSD3β2, aromatase, and HSD17β1) and estrogen receptors (ERα, ERβ, and GPER). Fibrosis was quantified via Masson trichrome staining. Real-time RT-PCR was performed to assess corresponding gene expression levels. The estrogen concentrations in cell cultures of primary stromal cells derived from different tissues were also measured by ELISA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Among all ectopic endometrial tissue samples, the extent of lesional fibrosis was the highest in the DE lesions, followed by the AD and then the OE lesions. The protein and gene expression levels of StAR, HSD3β2, aromatase, and HSD17β1, the four proteins critically involved in estrogen biosynthesis, were significantly higher than in the CT group in OE and AD lesions, but were lowest in DE lesions, which were comparable to that of c","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf028"},"PeriodicalIF":8.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia exposure impairs male fertility via inhibiting Septin2-mediated spermatogonial proliferation.","authors":"Zhibin Li, Shuying Li, Yufeng Xiao, Junfeng Guo, Jianchun Zhou, Yang Chen, Juan Yang, Chunli Gong, Bing He, Yuyun Wu, Nannan Gao, Huan Yang, Limin Gao, Hua Hu, Yunfang Zhang, Shiming Yang","doi":"10.1093/hropen/hoaf027","DOIUrl":"10.1093/hropen/hoaf027","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What are the molecular mechanisms underlying hypoxia-induced male reproductive impairment?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Hypoxia compromises Septin2 (&lt;i&gt;Sept2&lt;/i&gt;) transcription in spermatogonia, which impedes spermatogonial proliferation through protein phosphatase 2A (PP2A)-dependent AKT dephosphorylation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Hypoxia is associated with impaired spermatogenesis and poor sperm parameters in men. Spermatogonia proliferation, a crucial early step in spermatogenesis, is essential for maintaining the spermatogenic cell population and ensuring sperm quality. However, the connection between hypoxia and spermatogonial proliferation remains poorly understood, and treatment options for hypoxia-related reproductive disorders are limited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;A cross-sectional study analyzed semen samples from 24 high-altitude (HA) residents, 6 pathological hypoxia (PH) patients, and 19 healthy controls to evaluate hypoxia-associated sperm parameter alterations. Complementary animal studies employing a hypobaric chamber-induced hypoxic mouse model (n = 5) confirmed reproductive impairments through assessment of birth rates, sperm quality, and testicular histopathology. Transcriptomic profiling of hypoxic versus normoxic mouse testes (n = 3/group) identified spermatogonial proliferation defects as a predominant pathological feature and pinpointed &lt;i&gt;Sept2&lt;/i&gt; as a candidate mediator. Subsequent mechanistic investigations employed &lt;i&gt;in vitro&lt;/i&gt; hypoxic culture of spermatogonial cell lines under hypoxic conditions coupled with pharmacological modulation of PP2A activity in mice (n = 3-5 per intervention group) to delineate the underlying molecular pathways.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Semen parameters were evaluated using computer-assisted sperm analysis (CASA; for sperm concentration, count, and motility), morphological staining (Pap staining for sperm deformity), and eosin-nigrosin staining (for sperm viability). In the hypoxic mouse model, fertility outcomes were assessed through fertility assessment (mating experiments), sperm parameters (CASA), testicular histology (H&E staining), and spermatogonia proliferation (immunohistochemistry and qPCR). In hypoxic spermatogonial cell models, cell proliferation was detected using CCK-8, EdU incorporation, flow cytometry, and western blotting. &lt;i&gt;Sept2&lt;/i&gt; manipulation (knockdown/overexpression), followed by mechanistic analyses (dual-luciferase reporter assay, DNA pulldown/mass spectrometry, TMT-based quantitative proteomics, co-immunoprecipitation, etc.), was performed to investigate the mechanism underlying hypoxia-regulated spermatogonia proliferation. The SEPT2 inhibitor forchlorfenuron (FCF), the PP2A agonists celastrol, erlotinib, and FTY720, as well as PP2A inhibitor okadaic acid (OA) were used to investigate the role of the SEPT2-PP2A-AKT axis in male fer","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf027"},"PeriodicalIF":8.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of pubertal induction with combined gonadotropin therapy on testes development and spermatogenesis in males with gonadotropin deficiency: a cohort study.","authors":"Sebastian Castro, Kyla Ng Yin, Francesco d'Aniello, Emma C Alexander, Emily Connolly, Claire Hughes, Lee Martin, Rathi Prasad, Helen L Storr, Ruben H Willemsen, Leo Dunkel, Gary Butler, Sasha R Howard","doi":"10.1093/hropen/hoaf026","DOIUrl":"10.1093/hropen/hoaf026","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Are recombinant FSH (rFSH) and hCG effective therapies for promoting testicular growth and spermatogenesis in male adolescents and young adults with gonadotropin deficiency?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Combined gonadotropin therapy is effective in inducing puberty and promoting spermatogenesis in male adolescents and young adults with gonadotropin deficiency and has the potential to improve adult outcomes relating to both fertility and quality of life.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Deficiency of pituitary gonadotropins (LH and FSH) due to hypogonadotropic hypogonadism (HH) can result in poor testicular development, low testicular volumes, micropenis and cryptorchidism. Inadequate hormonal replacement can lead to long-term issues, including subfertility or infertility, and reduced quality of life. Exogenous testosterone for pubertal induction can elevate serum testosterone concentrations and induce virilization, but it does not promote testicular development nor induce spermatogenesis. Fertility and testes growth remain primary concerns for patients seeking treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;We conducted a retrospective observational review of male adolescents and young adults with gonadotropin deficiency and seeking puberty replacement therapy at two large tertiary centre hospitals in London, UK, from 2010 to 2024.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;A total of 35 males, with diagnosis of congenital hypogonadotropic hypogonadism (CHH: n = 23; further subdivided into those with partial [pHH: n = 8] and those with complete gonadotropin deficiency [cHH: n = 15]), acquired HH (AHH: n = 4) or Kallmann syndrome (KS: n = 8), received combined gonadotropin therapy. We assessed testicular growth and semen quality post-treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;The majority of patients were referred for pubertal delay, alone or in combination with cryptorchidism, micropenis or microorchidism. Out of 35 patients, 22 (63%) had previously received testosterone, and the median age at gonadotropin treatment initiation was 15.8 years (range: 11.8-22.7). Semen analysis was obtained in 18 out of 19 patients who had received gonadotropin therapy for a median treatment duration of 21.1 months (range: 4.5-66.9) for rFSH and 19.5 months (range: 8.3-61.1) for hCG. The median sperm count on semen analysis was 8.9 × 10&lt;sup&gt;6&lt;/sup&gt;/ml (range: 0.0-54.9). Significant increases were noted in testicular volume (median change after therapy: 10.5 ml [95% CI 9.5-13.6], &lt;i&gt;P&lt;/i&gt; &lt; 0.0001), testosterone (median increase: 25.7 nmol/l [95% CI 19.8-31.5], &lt;i&gt;P&lt;/i&gt; &lt; 0.0001) and inhibin B levels (67.7 pg/ml [95% CI 18.4-86.7], &lt;i&gt;P&lt;/i&gt; = 0.0008).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The relatively low representation of patients with acquired HH in our study emphasizes the need to extrapolate the findings with caution in thi","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf026"},"PeriodicalIF":8.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-year follow-up study (PRIMROSE 3) to assess bone mineral density in subjects with uterine fibroids completing the PRIMROSE 1 and PRIMROSE 2 linzagolix trials.","authors":"Jacques Donnez, Felice Petraglia, Hugh Taylor, Christian Becker, Sven Becker, Francisco Carmona Herrera, Maciej Paszkowski, Elke Bestel, Satoshi Hori, Marie-Madeleine Dolmans","doi":"10.1093/hropen/hoaf025","DOIUrl":"10.1093/hropen/hoaf025","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;How important was the change in lumbar spine (L1-L4), femoral neck, and total hip bone mineral density (BMD) from post-treatment baseline values to 24 months after the end of treatment in PRIMROSE 1 and PRIMROSE 2 study participants?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;In the present study (PRIMROSE 3), mean percentage changes in lumbar spine BMD from the post-treatment baseline to month 24 (primary endpoint) were small in most treatment groups and similar to variations in the placebo group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Due to its mechanism of action, some BMD decreases are observed with oral GnRH antagonist treatment, depending on the dose administered and addition or not of add-back therapy (ABT) (1 mg oestradiol and 0.5 mg norethisterone acetate). In PRIMROSE 1 and PRIMROSE 2, no significant changes in BMD were observed in any of the three anatomic sites investigated (lumbar spine, femoral neck, and total hip) in any of the treated groups but one. Indeed, at 24 weeks, mean differences were most pronounced in the lumbar spine in participants given 200 mg linzagolix alone.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;PRIMROSE 3 is a long-term follow-up study on BMD in subjects who completed at least 20 weeks of treatment in the main linzagolix trials (PRIMROSE 1 or PRIMROSE 2) and underwent dual-energy X-ray absorptiometry (DEXA) within 35 days of their last treatment (week 24 or week 52 [extension study]). The primary endpoint was the change in lumbar spine (L1-L4), femoral neck, and total hip BMD from post-treatment baseline values to 24 months after the end of treatment in PRIMROSE 1 and PRIMROSE 2 study participants. The secondary endpoint was the change in lumbar spine (L1-L4), femoral neck, and total hip BMD from pre-treatment baseline values to 24 months after the end of treatment. The study involved an eligibility visit and up to three follow-up consultations at 12, 18 and/or 24 months after the end of treatment in either PRIMROSE 1 or PRIMROSE 2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Patients given an end-of-treatment DEXA scan within 35 days of their last treatment were invited to participate in the PRIMROSE 3 study. Those who were pregnant or unable to undergo a DEXA scan on the same type of equipment as used for the end-of-treatment DEXA scan in PRIMROSE 1 or PRIMROSE 2 were not eligible for this trial. A total of 137 subjects were screened, 134 (97.8%) of whom were enrolled and 130 (94.9%) included in the safety analysis set. Subject groups were small and ranged from 7 subjects (placebo group) to 30 subjects (200 mg/200 mg+ABT group). Most subjects (n = 110, 80.3%) completed the study by evaluation of their BMD by DEXA at 2 years post-treatment.This study (EudraCT number: 2021-000452-19) was conducted at 3 sites in Bulgaria, 4 sites in the Czech Republic, 4 sites in Hungary, 1 site in Latvia, 6 sites in Poland, 1 site in Romania, 5 sites in Ukrain","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf025"},"PeriodicalIF":8.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}