Reproduction & fertility最新文献

{"title":"Ovarian puncture alters genes but not follicle growth in cyclophosphamide mice model.","authors":"Camila Stefane Ferreira, Luiza Aparecida Ansaloni Chagas Pereira, Stella Pollyanne de Oliveira, João Pedro Lobão Gomes de Castro, Vanessa Neves Guimarães, Patrick de Abreu Barbosa, Jade Carceroni de Sousa Carvalho, Ana Maria Alvarenga Fagundes, Antonio Sergio Varela Junior, Carine Dahl Corcini, Erika Cristina Jorge, Paulo Henrique Almeida Campos-Junior","doi":"10.1530/RAF-25-0192","DOIUrl":"10.1530/RAF-25-0192","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Cyclophosphamide administration often causes infertility. Ovarian puncture (OP), a component of in vitro fertilization, is performed to obtain oocytes. Our previous study showed that OP stimulated follicular activation in mice. However, its effects on folliculogenesis in cyclophosphamide-treated animals remain unclear. This study aimed to evaluate the impact of OP on follicular growth and gene expression. Female C57BL/06J mice (n = 52) were divided into three groups (control, cyclo, and cyclo + Pc). Cyclophosphamide was administered in four doses to the cyclo and cyclo + Pc groups (150 mg/kg), and OP was performed three days after the last dose and 96 h before euthanasia in the cyclo + Pc group. There was no difference in body weight; however, ovarian weight was higher in cyclo + Pc compared with cyclo. The number of all follicle classes was similar between cyclo + Pc and cyclo. Caspase-3-positive granulosa cells (%) in antral follicles were increased in cyclo compared with control and reduced in cyclo + Pc compared with control. Amh expression was increased in the cyclo + Pc group compared with the cyclo group. Pten expression was reduced in cyclo + Pc, whereas Kitl expression was increased. Bax expression was reduced, and there was no change in Casp3 expression due to OP. Moreover, collagen deposition was increased in cyclo + Pc compared with the control and cyclo groups. However, the treatments did not change the ovulation response, oocytes, or follicular morphometrics. Our experimental study demonstrates, for the first time, that OP is a safe procedure that can be performed during cyclophosphamide treatment in mice.</p><p><strong>Lay summary: </strong>Infertility is a concern for cancer patients who wish to conceive after completing chemotherapy treatment. Puncturing the ovary is part of the IVF procedure, aimed at collecting eggs to fertilize and transferring them to the uterus. We decided to study whether the inflammation and tissue damage caused by puncturing the ovaries could stimulate the collection of healthy eggs in patients who have gone through chemotherapy. To this end, we used female mice that were treated with a frequently used treatment for breast cancer, along with ovarian puncture. We discovered the alterations did not affect follicle growth or egg retrieval. With these findings, we demonstrated, for the first time, the ability of ovarian puncture to bring about healthy egg retrieval, improving quality of life after cancer.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868775","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":"Commonest causes of maternal mortality in Nigeria: a situational report requiring an urgent action.","authors":"Chukwuemeka Daniel Okolie, Archie Alexander, Matthew Kelley","doi":"10.1530/RAF-25-0144","DOIUrl":"10.1530/RAF-25-0144","url":null,"abstract":"<p><strong>Abstract: </strong>Maternal mortality remains a critical public health challenge in Nigeria, with rates far exceeding global targets. This narrative review correlates findings from peer-reviewed studies published between 2015 and 2025 to assess the burden, causes, and contributing factors of maternal mortality across Nigeria's six geopolitical zones. PubMed and Google Scholar were searched using predefined keywords, and studies reporting maternal mortality ratios (MMRs), causes of death, or contributing factors from Nigerian health facilities or population-based surveys were included. Hypertensive disorders of pregnancy (HDP) and obstetric hemorrhage were consistently identified as the leading direct causes of maternal death, while complications of unsafe abortion and sepsis were also prominent. Most of the non-medical contributing factors identified in this review study were poor utilization of prenatal care (PNC) services, limited access to healthcare facilities, financial constraints, and low educational attainment. Significant regional variation was observed, with facility-based MMRs ranging from 383 to 7,364 per 100,000 live births. This study emphasizes the urgent need for strengthened PNC delivery, improved emergency obstetric services, health workforce development, and targeted community health education to reduce maternal mortality in Nigeria.</p><p><strong>Lay summary: </strong>Deaths from pregnancy-related causes remain a major public health concern, especially in less developed countries. Nigeria is one of the countries with high pregnancy-related deaths. A substantial number of women who become pregnant in Nigeria never make it through the pregnancy. Our study investigated pregnancy-related deaths and their responsible factors across Nigeria. We found out that most of these deaths are caused by pregnancy-related bleeding, high blood pressure, and their complications. Pregnant women who do not attend prenatal care and those with low socioeconomic status are affected the most. Understanding the causes and contributing factors behind pregnancy-related deaths can help create ways to reduce this serious public health problem.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458302","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":"Unmet need for family planning among adolescent girls and young women (15-24 years) in Ethiopia during the FP2020 period: a propensity score matching analysis using PMA data.","authors":"Kaleb Assegid Demissie, Melak Jejaw, Getachew Teshale, Demiss Mulatu Geberu, Asebe Hagos, Nigusu Worku, Tesfahun Zemene Tafere, Endalkachew Dellie","doi":"10.1530/RAF-26-0022","DOIUrl":"10.1530/RAF-26-0022","url":null,"abstract":"<p><strong>Abstract: </strong>Adolescent and young women in Ethiopia have a high unmet need for family planning. The Family Planning 2020 strategy prioritized improving reproductive health among women aged 15-24 years. This study aims to assess the changes in the unmet need for family planning among adolescent and young women aged 15-24 years in Ethiopia during the Family Planning 2020 period. A cross-sectional pre-post study using propensity score matching analyzed two rounds of Performance Monitoring for Action data: 2014 (pre-family planning 2020) and 2021 (post-family planning 2020). Propensity score kernel matching was used, and covariate balance was assessed using standardized mean differences, median, and mean bias. A total of 3,128 adolescent and young women aged 15-24 years were included. The average treatment effect on the treated was estimated, and sensitivity analysis assessed robustness to hidden bias. The unmet need for family planning decreased from 22.9% (95% CI: 21.1-24.8) in 2014 to 17.8% (95% CI: 15.8-20.1) in 2021. Matching improved covariate balance, reducing mean bias (13.3-1.4), median bias (10.2-1.1), and standardized mean difference (58.8-5.8). The average treatment effect on the treated indicated a 2.5 percentage point reduction. Sensitivity analysis using Rosenbaum bounds showed that the effect remained significant up to Γ = 2 (P < 0.0001), indicating robustness to hidden bias. The unmet need for family planning among Ethiopian adolescent and young women aged 15-24 years has declined. Continued efforts under the Family Planning 2030 strategy are needed to sustain and further improve access to family planning services.</p><p><strong>Lay summary: </strong>Adolescent and young women in Ethiopia still face serious challenges in family planning. The FP2020 strategy was designed to improve the family planning experience for women between the ages of 15 and 24 years. This study seeks to evaluate the effect of the strategy on unmet needs of women for family planning by carrying out an assessment of data collected from national surveys conducted before the strategy was established in 2014 and after the establishment of the strategy in 2021. The data show that unmet needs for family planning have reduced since the establishment of the strategy. After the analysis of the variance between the study groups, the study found that there is a reduction in unmet needs for family planning. However, unmet needs remain, meaning that many young women still face challenges in obtaining contraception and making informed reproductive choices. Commitment to the new strategy, that is FP2030, is required for the improvement of family planning access and use for young women.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13482794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148595437","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":"Response: Rectovaginal septum is a real location for deep endometriosis; comment on the article: 'the myth of rectovaginal septum endometriosis'.","authors":"Mathew Leonardi, Shay M Freger","doi":"10.1530/RAF-26-0116","DOIUrl":"10.1530/RAF-26-0116","url":null,"abstract":"","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458116","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":"The maternal immune response to semen: implications for reproductive success in livestock.","authors":"Sophie Warr, Taylor Pini, Simon P de Graaf, Jessica P Rickard","doi":"10.1530/RAF-26-0039","DOIUrl":"10.1530/RAF-26-0039","url":null,"abstract":"<p><strong>Abstract: </strong>Following semen deposition, the female reproductive tract must balance immune tolerance towards spermatozoa with preservation of antimicrobial defence. To date, much of our understanding of female immune response following insemination has been derived from models of pathogen defence and uterine receptivity in humans, with comparatively little on how these same immune pathways shape successful sperm transport. Here, we summarise the relationship between early sperm transport immediately following semen deposition and acute innate immune activation, characterised by complement engagement and rapid leukocyte recruitment. Polymorphonuclear neutrophils, traditionally viewed as terminal effectors of sperm clearance, are reframed as active mediators of innate surveillance and sperm immune adaptation. Spermatozoa enter the female environment bearing a molecular identity shaped by testicular development, epididymal maturation, and exposure to seminal plasma, yet the link between specific mediators, immunity, and fertility has yet to be explored in livestock. Seminal plasma extracellular vesicles stand out as a promising mediator of complement activity and cytokine signalling. Disruption of this male-derived immune conditioning through processing for cryopreservation is hypothesised to explain impaired sperm transport in sheep. Orchestrating male and female contributions to the maternal immune response reframes reproductive success as coordinated sperm-immune communication. This review identifies knowledge gaps whose resolution will advance our understanding of immune tolerance to spermatozoa, informing strategies to enhance the success of assisted reproductive technologies in livestock.</p><p><strong>Lay summary: </strong>Successful reproduction requires a highly functional immune response to defend against pathogens while facilitating sperm transport. This review explores how sperm and seminal plasma actively communicate with the female immune system immediately following semen deposition. We highlight how immune cells and complement proteins shape sperm survival, and how alterations to the sperm immune profile during in vitro processing may disrupt this delicate balance of communication within the female.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475472","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":"Role of oral gonadotropin-releasing hormone antagonists in the management of uterine adenomyosis: a narrative review.","authors":"Jacques Donnez, Olivier Donnez, Hugh S Taylor, Felice Petraglia, Andrew W Horne, Christian M Becker, Stefan P Renner, Marionna Rius, Elke Bestel, Christina Anna Stratopoulou, Marie-Madeleine Dolmans","doi":"10.1530/RAF-26-0075","DOIUrl":"10.1530/RAF-26-0075","url":null,"abstract":"<p><strong>Abstract: </strong>In women with uterine adenomyosis, bleeding and pain can have a major impact on quality of life. There is clearly a widespread demand for effective long-term medical therapies. The objective of this narrative review was to investigate the efficacy of oral gonadotropin-releasing hormone (GnRH) antagonists in the management of uterine adenomyosis by analyzing data from two post hoc analyses of two prospective randomized trials (elagolix and relugolix), one retrospective study (relugolix) and one prospective study (linzagolix). All three GnRH oral antagonists were able to control the disease and uterine fibroid-related heavy menstrual bleeding, enhancing quality of life. When administered without add-back therapy, high doses of GnRH antagonists were found to significantly and rapidly reduce uterine volume and the severity of adenomyotic lesions. Nevertheless, some limitations should be addressed. The post hoc analyses were a retrospective look at two prospective randomized clinical trials. In the elagolix study, most women underwent both transvaginal ultrasound and magnetic resonance imaging (MRI). Some who opted out of MRI may have had concurrent adenomyosis that was undetected by ultrasound, so they were not included in the adenomyosis subset. In the relugolix study, baseline ultrasounds were not specifically performed to spot adenomyosis that may have been overlooked in case of large fibroids, as shadowing can partially or completely obscure the disease. While the linzagolix study is prospective and evaluates data from women with proven adenomyosis documented by MRI, the number of cases is limited and randomized controlled trials are needed to confirm and validate this concept.</p><p><strong>Lay summary: </strong>Uterine adenomyosis is characterized by the presence of endometrial glands inside the myometrium, the muscular layer of the uterus. Transvaginal ultrasound and magnetic resonance imaging now facilitate its diagnosis. The estimated prevalence of adenomyosis among patients of reproductive age is 20-30%. Rising rates in younger patients combined with a growing trend to postpone first pregnancy underscore the importance of understanding the mechanisms behind its development. We need novel strategies for the treatment of typical but distressing symptoms of adenomyosis, which include pelvic pain, abnormal uterine bleeding, menstrual cramps, painful sex and infertility. There is a lack of approved pharmacological agents specifically indicated for the treatment of adenomyosis, presenting a clear unmet need in this population. Oral gonadotropin-releasing hormone (GnRH) antagonists have recently emerged as a promising new therapeutic option. Their advantages over GnRH agonist depot formulations include an absence of the flare-up effect, hence avoiding initially worsening symptoms and rapid reversibility.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761931","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":"The association of endometrial thickness with live birth: a differential impact of agonist vs antagonist ovarian stimulation protocols.","authors":"Ruowu Ma, Xiaohui Ji, Xiangping Zhu, Meiqing Xie, Qingxue Zhang","doi":"10.1530/RAF-25-0050","DOIUrl":"10.1530/RAF-25-0050","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>To explore the relationship between endometrium, quality of transferred embryo, and their effects on the live birth outcome of IVF/ICSI-ET using different downregulation protocols, we conducted a retrospective cohort study in an academic reproductive medical center. A total of 13,585 participant's first fresh embryo transfer cycles, comprising 10,951 cycles using the GnRH-agonist regimen and 2,634 cycles using the GnRH-antagonist regimen, were included in this study. We found that the first fresh embryo transfer cycles using the GnRH-agonist downregulation regimen achieved a significantly improved live birth rate (41.9%) compared with the fresh cycles using the GnRH-antagonist regimen (30.4%). This was accompanied by a significantly thicker endometrium on the day of hCG administration. In the general population, increased endometrial thickness in the agonist group demonstrated a protective effect on the live birth. The cutoff value of endometrial thickness for live birth increased with the addition of poor-quality embryos in the double cleavage-stage embryo transfer cycles and the single blastocyst transfer cycles. Different choices of downregulation strategy affect the endometrium and the treatment outcome of IVF/ICSI-ET.</p><p><strong>Lay summary: </strong>The union of an embryo and the uterine lining is much like that of a seed and soil. The process of nurturing life resembles a seed taking root, sprouting, and bearing fruit. Different seeds require different conditions and soils. In assisted reproductive technology, the downregulation protocol used can affect the state of the uterine lining. Embryos of varying quality also have different chances of successful implantation. Just as fertile soil supports a seed's growth, an endometrium of suitable thickness favors embryo implantation. When seed quality is less than ideal, a richer soil may improve its chance to take root. Similarly, when the available embryos are of lower quality, a thicker endometrial lining is associated with a higher live birth rate.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763462","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":"Late-follicular androgen and estrogen rise associated with clinical pregnancy in IVF/ICSI with granulosa cell studies.","authors":"Rungnapa Sririwichitchai, Chantacha Sitticharoon, Issarawan Keadkraichaiwat, Pailin Maikaew, Suchawadee Chanheng, Somsin Petyim","doi":"10.1530/RAF-26-0062","DOIUrl":"10.1530/RAF-26-0062","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Graphical abstract: &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Abstract: &lt;/strong&gt;This study aimed to characterize phase-specific dynamics of androstenedione and estradiol across IVF/ICSI treatment, identify predictors of reproductive outcomes, and examine the effects of follicle-stimulating hormone (FSH), IGF1, and estradiol on steroidogenesis in human granulosa-like tumor (KGN) cells. In women undergoing IVF/ICSI (10 successful and 19 unsuccessful), serum hormones were measured before recombinant FSH stimulation (Phase 1) and during the mid-follicular (Phase 2) and ovulatory (Phase 3) phases, with follicular fluid (FF) collected at Phase 3. Mechanistic experiments were conducted in KGN cells (n = 3) treated for 24 h. Successful pregnancy was associated with greater increases in androstenedione and estradiol from Phase 2 to Phase 3 and higher Phase 3 steroid-to-basal gonadotropin ratios. Elevated Phase 1 androstenedione and estradiol were negatively correlated with the number of retrieved oocytes, mature oocytes, and/or embryos. Phase 3 serum androstenedione (cutoff ≥ 2.382 ng/mL; AUC = 0.708, P = 0.038) and FF aromatase (cutoff ≤ 0.378 ng/mL; AUC = 0.727, P = 0.007) predicted clinical pregnancy. In KGN cells, IGF1 stimulated early steroidogenesis (HSD3B2 mRNA expression and progesterone levels), FSH enhanced both early and late pathways (HSD3B2 and CYP19A1 mRNA expression together with progesterone, androstenedione, and aromatase levels), and supraphysiological estradiol suppressed downstream steroidogenesis (CYP19A1 mRNA expression and aromatase and progesterone levels). In conclusion, a favorable pattern with low early-follicular and high late-follicular androstenedione and estradiol was associated with IVF/ICSI success, whereas high early androstenedione and estradiol appeared detrimental. In KGN cells, supraphysiological estradiol without androgen substrate suppressed downstream steroidogenesis, consistent with the adverse effects of excessive early estradiol exposure, supporting granulosa cell contribution to local androgen availability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Lay summary: &lt;/strong&gt;Fertility treatment does not always lead to pregnancy. Hormones produced by the ovaries play a key role in pregnancy success. However, it is not clear how hormonal changes over time affect pregnancy. To address this gap, we followed up women undergoing fertility treatment and measured key reproductive hormones, including androstenedione (A4) and estradiol (E2), at different stages of the treatment cycle. We also used human ovarian cells to understand how E2 influences hormone production. We found that women who became pregnant showed a clear rise in A4 and E2 just before ovulation, while women who did not become pregnant had higher hormone levels at the beginning of the cycle. Our study in human ovarian cells supported these results, showing that excessive early A4 and E2 exposure could reduce later hormone production. Our findings may improve the prediction of treatment success","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458125","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":"Impact of gender-affirming hormone therapy on the endocrine axis and male germ cells.","authors":"Karen Schiwon, Florian Sieg, Florian Schneider, Jochen Hess, Sabine Kliesch, Stefan Schlatt, Sara Di Persio, Nina Neuhaus","doi":"10.1530/RAF-26-0032","DOIUrl":"10.1530/RAF-26-0032","url":null,"abstract":"<p><strong>Abstract: </strong>Gender-affirming hormone therapy (GAHT) facilitates the desired phenotypic changes consistent with an individual's gender identity. However, inter-individual variability in treatment effects has been reported at the endocrine and testicular tissue levels. To address the hypothesis that treatment effects are not homogeneous, we selected 24 persons from a cohort of 453 persons assigned male at birth, based on a similar dose of cyproterone acetate (Androcur®, 10 or 12.5 mg/day). Principal component analysis and hierarchical clustering on principal components were performed considering clinical parameters and identified four distinct clusters. Cluster 1 (n = 3) was characterized by the presence of tubules with round or elongated spermatids, the highest numbers of reserve spermatogonia (Adark) and cells positive for UTF1, PIWIL4, NANOS3 and KIT. Persons in Cluster 2 (n = 4) showed a high percentage of tubules with spermatogonia as the most advanced germ cell type and high testosterone levels that were not suppressed to the desired female values. Persons in Cluster 3 (n = 10) had low testosterone but elevated AMH levels and suppressed spermatogenesis to the spermatogonial level. Finally, persons in Cluster 4 (n = 7) had the highest number of Sertoli cell-only tubules and tubular shadows, as well as the highest person age. Despite homogeneous inclusion criteria, we observed heterogeneous treatment effects. Consultation regarding contraceptives, as well as fertility preservation, therefore has to be considered in counselling, ideally prior to initiation of GAHT.</p><p><strong>Lay summary: </strong>Hormonal therapy can help to align one's physical appearance with gender identity. However, hormonal therapy does not work the same way for everyone. The effects on testis function, including hormone and sperm production, can vary considerably. In this study, we characterized persons who received comparable therapies to transition to their desired female gender. We found four subgroups: in Group 1, sperm was still produced by testicular tissues. In Group 2, only precursors of sperm were present, but male, rather than the desired female, hormone levels were observed. In Group 3, only precursors of sperm were present, and desired hormone levels were reached. Finally, Group 4 largely showed loss of germ cells and included the oldest people in the study. These results are relevant for counselling, as individuals need to be informed about the different effects that hormonal therapy can have with regard to sperm production and thereby fertility.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703270","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":"Trophoblast stem cells and syncytiotrophoblasts lack inflammatory responses to LPS but retain robust interferon-mediated antiviral immunity.","authors":"Cristine R Camp, Joshua Baskaran, Matthew Brown, Carly Parker, Paige Drotos, Rachel C West","doi":"10.1530/RAF-25-0176","DOIUrl":"10.1530/RAF-25-0176","url":null,"abstract":"<p><strong>Abstract: </strong>Early pregnancy requires a tightly regulated pro-inflammatory environment shared between the primitive placenta and decidua. While immune balance supports successful implantation and placental invasion, disruptions in immune signaling during this period can impair implantation and lead to embryo loss. In this study, we investigated the molecular mechanisms underlying immune imbalance during implantation using a trophoblast stem cell (TSC) model. TSCs were cultured in either stem cell or syncytiotrophoblast (STB) differentiation medium and treated with either lipopolysaccharides (LPSs) or interferon beta (IFNB). RT-qPCR and western blotting revealed that LPS failed to induce a pro-inflammatory cytokine response in TSCs or STBs. In contrast, IFNB triggered a strong antiviral response in both TSCs and STBs. RNA sequencing of IFNB-treated TSC and STB 3D spheroids revealed subtle differences between the TSC and STB responses to interferons. Both TSC and STB IFNB-treated spheroids mount an interferon-mediated antiviral response; however, STB spheroid genes associated with the type I interferon response, viral RNA/DNA sensing, and antigen processing were upregulated. We also compared the interferon response between the CT27 (female) and CT29 (male) TSCs and STBs. While STBs showed minimal differences, the CT29 TSCs exhibited a markedly stronger interferon response than the CT27 TSCs. Collectively, these findings suggest that the primitive placenta is selectively responsive to interferon signaling rather than direct pathogen-associated stimuli. This implies that maternal immune activation, rather than microbial invasion, likely drives that placental immune response and embryo success at this stage. Understanding these dynamics underscores the importance of the maternal immune balance in early pregnancy success.</p><p><strong>Lay summary: </strong>The maternal immune system has a direct influence on the success of embryo implantation. If that balance is disturbed, the placenta can fail to invade into the uterus and implantation can fail, leading to embryo mortality and pregnancy loss. In our study, we used stem cells from the placenta to explore how they respond to different kinds of immune signals (i.e. signals from bacteria versus signals from the mother's immune response). We found that placental stem cells do not respond to signals from bacteria. However, they do react strongly to signals that resemble a viral infection in the mother. These data suggest that the early placenta is more sensitive to the mother's immune signals than to direct infection, which highlights the critical role of maternal immune health in early pregnancy.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304453","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}