The preservation of spermatozoa through cryopreservation is a cornerstone of reproductive medicine, genetic biodiversity conservation and biomedical research. Traditionally, liquid nitrogen (LN2) storage at –196°C has been considered the gold standard for sperm biobanking. The high costs, logistical challenges and safety concerns associated with LN2, however, have prompted a reevaluation of alternative cryopreservation methods. This review traces the historical evolution of sperm cryopreservation, from its inception in 1938 to modern technological advancements, and proposes a paradigm shift towards ultra-low freezers operating at –80°C.
Emerging evidence suggests that ultra-low freezers offer a cost-effective, sustainable and accessible alternative for sperm biobanking, particularly benefiting research institutions in low- and middle-income countries. Comparative analyses indicate that spermatozoa stored at –80°C retain fertilization potential over extended periods, challenging long-standing assumptions about the necessity of LN2. Additionally, the integration of cryoprotectants and antioxidants could further enhance the viability of spermatozoa stored in ultra-low freezers, mitigating concerns about DNA integrity and oxidative stress. By decentralizing sperm biobanking and reducing dependence on LN2, this approach fosters a more inclusive, resilient and environmentally sustainable system for the preservation of genetic resources.
{"title":"From –196°C to –80°C: redefining standards in sperm biobanking technology","authors":"Costanza Cimini , Marina Ramal-Sanchez , Luca Valbonetti , Renata Paoletti , Marcello Raspa , Alessia Colosimo , Ferdinando Scavizzi , Nicola Bernabò , Barbara Barboni","doi":"10.1016/j.rbmo.2025.105180","DOIUrl":"10.1016/j.rbmo.2025.105180","url":null,"abstract":"<div><div>The preservation of spermatozoa through cryopreservation is a cornerstone of reproductive medicine, genetic biodiversity conservation and biomedical research. Traditionally, liquid nitrogen (LN2) storage at –196°C has been considered the gold standard for sperm biobanking. The high costs, logistical challenges and safety concerns associated with LN2, however, have prompted a reevaluation of alternative cryopreservation methods. This review traces the historical evolution of sperm cryopreservation, from its inception in 1938 to modern technological advancements, and proposes a paradigm shift towards ultra-low freezers operating at –80°C.</div><div>Emerging evidence suggests that ultra-low freezers offer a cost-effective, sustainable and accessible alternative for sperm biobanking, particularly benefiting research institutions in low- and middle-income countries. Comparative analyses indicate that spermatozoa stored at –80°C retain fertilization potential over extended periods, challenging long-standing assumptions about the necessity of LN2. Additionally, the integration of cryoprotectants and antioxidants could further enhance the viability of spermatozoa stored in ultra-low freezers, mitigating concerns about DNA integrity and oxidative stress. By decentralizing sperm biobanking and reducing dependence on LN2, this approach fosters a more inclusive, resilient and environmentally sustainable system for the preservation of genetic resources.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 2","pages":"Article 105180"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145842367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-09-09DOI: 10.1016/j.rbmo.2025.105260
Trang Thao Vu , Khanh Thi Mai Nguyen , Huong Thi Thu Hoang , Truc Nhu Thanh Vo
Research question
Is there a difference in embryo development potential between fresh oocytes and cryopreserved oocytes from the same patient, when both are subjected to the same conditions for fertilization and culture?
Design
A retrospective matched comparative cross-sectional analysis was conducted on 239 autologous oocyte IVF cycles (2138 fresh and 1259 frozen oocytes) between March and October 2024. In total, 3002 oocytes (1743 fresh mature oocytes and 1195 surviving warmed oocytes) were included in the analysis. Subgroup analyses were performed based on maternal age, oocyte morphological abnormalities and semen quality to further explore differences in embryological outcomes.
Results
The development potential of fresh oocytes was significantly higher than that of frozen oocytes, as shown by the cleavage-stage embryo rate (median 67.81% versus 59.90%), good-quality cleavage-stage embryo rate (74.38% versus 64.79%), blastocyst formation rate (42.66% versus 28.25%), and good-quality blastocyst rate (34.04% versus 20.97%) (all P ≤ 0.005). Subgroup analyses also supported superior blastocyst development from fresh oocytes (P < 0.05). Multivariate regression showed that factors such as maternal age, semen quality, and oocyte or sperm morphology did not influence outcomes significantly, indicating minimal bias in the analysis.
Conclusions
To the authors’ knowledge, this is the first study to apply a retrospective, matched, comparative cross-sectional design to compare the development potential of autologous fresh and frozen oocytes under identical intracytoplasmic sperm injection and culture conditions. The results suggest that to achieve the best outcomes in IVF cycles, the decision to freeze oocytes should be personalized, considering each patient's unique characteristics, especially in women of advanced maternal age.
{"title":"Blastocyst development potential in fresh versus vitrified oocytes: a retrospective matched comparative cross–sectional study","authors":"Trang Thao Vu , Khanh Thi Mai Nguyen , Huong Thi Thu Hoang , Truc Nhu Thanh Vo","doi":"10.1016/j.rbmo.2025.105260","DOIUrl":"10.1016/j.rbmo.2025.105260","url":null,"abstract":"<div><h3>Research question</h3><div>Is there a difference in embryo development potential between fresh oocytes and cryopreserved oocytes from the same patient, when both are subjected to the same conditions for fertilization and culture?</div></div><div><h3>Design</h3><div>A retrospective matched comparative cross-sectional analysis was conducted on 239 autologous oocyte IVF cycles (2138 fresh and 1259 frozen oocytes) between March and October 2024. In total, 3002 oocytes (1743 fresh mature oocytes and 1195 surviving warmed oocytes) were included in the analysis. Subgroup analyses were performed based on maternal age, oocyte morphological abnormalities and semen quality to further explore differences in embryological outcomes.</div></div><div><h3>Results</h3><div>The development potential of fresh oocytes was significantly higher than that of frozen oocytes, as shown by the cleavage-stage embryo rate (median 67.81% versus 59.90%), good-quality cleavage-stage embryo rate (74.38% versus 64.79%), blastocyst formation rate (42.66% versus 28.25%), and good-quality blastocyst rate (34.04% versus 20.97%) (all <em>P</em> ≤ 0.005). Subgroup analyses also supported superior blastocyst development from fresh oocytes (<em>P</em> < 0.05). Multivariate regression showed that factors such as maternal age, semen quality, and oocyte or sperm morphology did not influence outcomes significantly, indicating minimal bias in the analysis.</div></div><div><h3>Conclusions</h3><div>To the authors’ knowledge, this is the first study to apply a retrospective, matched, comparative cross-sectional design to compare the development potential of autologous fresh and frozen oocytes under identical intracytoplasmic sperm injection and culture conditions. The results suggest that to achieve the best outcomes in IVF cycles, the decision to freeze oocytes should be personalized, considering each patient's unique characteristics, especially in women of advanced maternal age.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 2","pages":"Article 105260"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-08-22DOI: 10.1016/j.rbmo.2025.105230
Silke Dyer , Liezel Potgieter , Frissiano Honwana , Eman Elgindy , Rudolph Kantum Adageba , Mohamed Khrouf , Jean Claude Kolani , Faye Iketubosin , Paul Le Roux , Paversan Archary , African Network and Registry for Assisted Reproductive Technology
Research question
What were the utilization, effectiveness and safety of assisted reproductive technology (ART) in Africa in 2021 and 2022?
Design
Cross-sectional cycle-based data collected from voluntarily participating centres.
Results
Data were reported by 63 centres in 14 countries in 2021, and 69 centres in 16 countries in 2022. In 2021, there were 26,481 autologous aspirations and 29,523 autologous transfers (58.8% fresh transfers), 2681 transfers after oocyte donation, and 2074 cycles utilizing preimplantation genetic testing (PGT). In 2022, there were 31,596 autologous aspirations and 35,109 autologous transfers (55.8% fresh transfers), 3393 transfers after oocyte donation, and 2297 cycles utilizing PGT. In both years, the mean age of women undergoing autologous fresh transfers was 34 years, with a mean number of 2.3 embryos per transfer. In 2021, the pregnancy rate was 38.1% per fresh transfer and 41.9% per frozen embryo transfer, with a cumulative pregnancy rate per aspiration of 44.2%. In 2022, these rates were 36.5%, 42.6% and 43.6%, respectively. In total, 16,549 pregnancies were lost to follow-up. Based on reported outcomes, the multiple delivery rate was ≥20% following most procedures. Most multiples were born preterm and had substantially increased perinatal mortality compared with singletons. Elective single embryo transfer provided the best balance of ART effectiveness and safety. Ten-year trends documented stable effectiveness in fresh cycles, increasing effectiveness in frozen cycles, and no decline in multiple delivery rates.
Conclusion
This report marks the 10th anniversary of the African Network and Registry for Assisted Reproductive Technology (ANARA). ANARA’s annual reports represent and critically inform regional ART development based on real-world evidence and national, regional and global cooperation.
{"title":"Assisted reproductive technology in Africa: the African Network and Registry for ART, 2021 and 2022","authors":"Silke Dyer , Liezel Potgieter , Frissiano Honwana , Eman Elgindy , Rudolph Kantum Adageba , Mohamed Khrouf , Jean Claude Kolani , Faye Iketubosin , Paul Le Roux , Paversan Archary , African Network and Registry for Assisted Reproductive Technology","doi":"10.1016/j.rbmo.2025.105230","DOIUrl":"10.1016/j.rbmo.2025.105230","url":null,"abstract":"<div><h3>Research question</h3><div>What were the utilization, effectiveness and safety of assisted reproductive technology (ART) in Africa in 2021 and 2022?</div></div><div><h3>Design</h3><div>Cross-sectional cycle-based data collected from voluntarily participating centres.</div></div><div><h3>Results</h3><div>Data were reported by 63 centres in 14 countries in 2021, and 69 centres in 16 countries in 2022. In 2021, there were 26,481 autologous aspirations and 29,523 autologous transfers (58.8% fresh transfers), 2681 transfers after oocyte donation, and 2074 cycles utilizing preimplantation genetic testing (PGT). In 2022, there were 31,596 autologous aspirations and 35,109 autologous transfers (55.8% fresh transfers), 3393 transfers after oocyte donation, and 2297 cycles utilizing PGT. In both years, the mean age of women undergoing autologous fresh transfers was 34 years, with a mean number of 2.3 embryos per transfer. In 2021, the pregnancy rate was 38.1% per fresh transfer and 41.9% per frozen embryo transfer, with a cumulative pregnancy rate per aspiration of 44.2%. In 2022, these rates were 36.5%, 42.6% and 43.6%, respectively. In total, 16,549 pregnancies were lost to follow-up. Based on reported outcomes, the multiple delivery rate was ≥20% following most procedures. Most multiples were born preterm and had substantially increased perinatal mortality compared with singletons. Elective single embryo transfer provided the best balance of ART effectiveness and safety. Ten-year trends documented stable effectiveness in fresh cycles, increasing effectiveness in frozen cycles, and no decline in multiple delivery rates.</div></div><div><h3>Conclusion</h3><div>This report marks the 10<sup>th</sup> anniversary of the African Network and Registry for Assisted Reproductive Technology (ANARA). ANARA’s annual reports represent and critically inform regional ART development based on real-world evidence and national, regional and global cooperation.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 2","pages":"Article 105230"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-02-04DOI: 10.1016/j.rbmo.2025.104858
Viktoria Christoforaki , Christos Venetis , Dimitrios G. Goulis , Leonidas Zepiridis , Katerina Chatzimeletiou , Anna Mitsoli , Despoina Savvaidou , Grigoris Grimbizis , Efstratios M. Kolibianakis
This systematic review/meta-analysis was conducted using MEDLINE, CENTRAL, Embase and randomized controlled trial registries up to December 2024. The study evaluated whether seminal oxidation-reduction potential (ORP), as a marker of oxidative stress, differs between fertile men and men with infertility, and whether it is associated with semen quality.
Thirteen studies were included in the meta-analysis, showing lower ORP levels in fertile men compared with men with infertility [(weighted mean difference (WMD) -4.07, 95% CI -5.80 to -2.35], and in patients with normal semen parameters compared with patients with at least one abnormal semen parameter (WMD -2.39, 95% CI -4.01 to -0.76). Patients with high ORP levels had a lower sperm concentration (WMD -35.76, 95% CI -52.40 to -19.11), total sperm count (WMD -126.41, 95% CI -208.59 to -44.22), total motility (WMD -8.80, 95% CI -11.17 to -6.44), progressive motility (WMD -7.62, 95% CI -10.74 to -4.49) and percentage of normal morphology (WMD -1.55, 95% CI -1.93 to -1.16); and a higher proportion of immotile spermatozoa (WMD +8.46, 95% CI +1.67 to +15.26) compared with patients with low ORP levels. In conclusion, seminal ORP levels are negatively associated with male fertility, sperm concentration, total sperm count, total and progressive motility, and normal morphology; and positively associated with immotile spermatozoa.
该系统评价/荟萃分析使用MEDLINE、CENTRAL、Embase和随机对照试验注册中心进行，截止到2024年12月。该研究评估了作为氧化应激标志的精液氧化还原电位（ORP）在有生育能力的男性和不育男性之间是否存在差异，以及它是否与精液质量有关。荟萃分析纳入了13项研究，结果显示，与不育男性相比，可生育男性的ORP水平较低[(加权平均差(WMD) -4.07, 95% CI -5.80至-2.35]，精液参数正常的患者与至少有一项精液参数异常的患者相比，ORP水平较低（WMD -2.39, 95% CI -4.01至-0.76）。ORP水平高的患者有较低的精子浓度（WMD -35.76, 95% CI -52.40 ~ -19.11）、总精子数（WMD -126.41, 95% CI -208.59 ~ -44.22）、总运动力（WMD -8.80, 95% CI -11.17 ~ -6.44）、渐进运动力（WMD -7.62, 95% CI -10.74 ~ -4.49）和正常形态百分比（WMD -1.55, 95% CI -1.93 ~ -1.16）；与ORP水平较低的患者相比，不动精子比例更高（WMD +8.46, 95% CI +1.67 ~ +15.26）。综上所述，精液ORP水平与男性生育能力、精子浓度、精子总数、总活力和渐进活力以及正常形态呈负相关；而且与精子不动呈正相关。
{"title":"The role of seminal oxidation-reduction potential in male infertility: systematic review and meta-analysis","authors":"Viktoria Christoforaki , Christos Venetis , Dimitrios G. Goulis , Leonidas Zepiridis , Katerina Chatzimeletiou , Anna Mitsoli , Despoina Savvaidou , Grigoris Grimbizis , Efstratios M. Kolibianakis","doi":"10.1016/j.rbmo.2025.104858","DOIUrl":"10.1016/j.rbmo.2025.104858","url":null,"abstract":"<div><div>This systematic review/meta-analysis was conducted using MEDLINE, CENTRAL, Embase and randomized controlled trial registries up to December 2024. The study evaluated whether seminal oxidation-reduction potential (ORP), as a marker of oxidative stress, differs between fertile men and men with infertility, and whether it is associated with semen quality.</div><div>Thirteen studies were included in the meta-analysis, showing lower ORP levels in fertile men compared with men with infertility [(weighted mean difference (WMD) -4.07, 95% CI -5.80 to -2.35], and in patients with normal semen parameters compared with patients with at least one abnormal semen parameter (WMD -2.39, 95% CI -4.01 to -0.76). Patients with high ORP levels had a lower sperm concentration (WMD -35.76, 95% CI -52.40 to -19.11), total sperm count (WMD -126.41, 95% CI -208.59 to -44.22), total motility (WMD -8.80, 95% CI -11.17 to -6.44), progressive motility (WMD -7.62, 95% CI -10.74 to -4.49) and percentage of normal morphology (WMD -1.55, 95% CI -1.93 to -1.16); and a higher proportion of immotile spermatozoa (WMD +8.46, 95% CI +1.67 to +15.26) compared with patients with low ORP levels. In conclusion, seminal ORP levels are negatively associated with male fertility, sperm concentration, total sperm count, total and progressive motility, and normal morphology; and positively associated with immotile spermatozoa.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 2","pages":"Article 104858"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-06-03DOI: 10.1016/j.rbmo.2025.105080
T. Lee , F. Qi , K. Peirce , J. Natalwala , V. Chapple , P.J. Mark , K. Sanders , Y. Liu
Unlike embryos that display two pronuclei (2PN), monopronucleated (1PN) embryos are assumed to be haploid and can be routinely discarded. Although there are reports of live births after 1PN embryo transfer, the developmental and clinical prognosis of 1PN embryos has not been systematically evaluated. The aim of this review was to elucidate the developmental, clinical and neonatal outcomes of 1PN embryos compared with 2PN embryos. Twenty-four studies met the inclusion criteria. The blastulation rate was lower in 1PN embryos compared with 2PN embryos [risk ratio (RR) 0.50, 95% CI 0.48–0.51]. The live birth rate was lower in 1PN blastocysts when untested (RR 0.81, 95% CI 0.72–0.90), but was similar after euploidy confirmation by preimplantation genetic testing for aneuploidy (RR 0.85, 95% CI 0.59–1.23). The euploidy rate was comparable in 1PN and 2PN embryos (RR 0.91, 95% CI 0.81–1.02). In a subgroup analysis of untested embryos, 1PN-intracytoplasmic sperm injection (ICSI) blastocysts had a lower live birth rate compared with 2PN-ICSI blastocysts (RR 0.26, 95% CI 0.13–0.50), while no difference was observed with IVF (RR 0.93, 95% CI 0.82–1.06). These results are particularly important for patients with a poor prognosis and limited 2PN embryos, and can aid reproductive professionals to counsel patients on the clinical use of 1PN embryos. Future studies should utilise time-lapse and preimplantation genetic testing technologies for confirmation of diploidy and biparental inheritance. Monopronucleated embryos can be viable, expanding options beyond 2PN embryos.
与显示两个原核（2PN）的胚胎不同，单核（1PN）胚胎被认为是单倍体，可以常规丢弃。虽然有1PN胚胎移植后活产的报道，但尚未对1PN胚胎的发育和临床预后进行系统评估。本综述的目的是阐明1PN胚胎与2PN胚胎的发育、临床和新生儿结局。24项研究符合纳入标准。1PN胚胎的囊胚率低于2PN胚胎[风险比（RR） 0.50, 95% CI 0.48-0.51]。未检测1PN囊胚的活产率较低（RR 0.81, 95% CI 0.72-0.90），但通过植入前基因检测确认非整倍体的整倍性后，活产率相似（RR 0.85, 95% CI 0.59-1.23）。1PN和2PN胚胎的整倍体率相当（RR 0.91, 95% CI 0.81-1.02）。在未检测胚胎的亚组分析中，1pn -胞浆内单精子注射（ICSI）囊胚的活产率比2PN-ICSI囊胚低（RR 0.26, 95% CI 0.13-0.50），而与IVF囊胚无差异（RR 0.93, 95% CI 0.82-1.06）。这些结果对于预后不良和2PN胚胎有限的患者尤为重要，可以帮助生殖专业人员为临床使用1PN胚胎的患者提供建议。未来的研究应利用延时和植入前基因检测技术来确认二倍体和双亲本遗传。单核胚胎可以存活，扩大了2PN胚胎的选择范围。
{"title":"To discard or not to discard 1PNs? A systematic review and meta-analysis on 291,474 embryos","authors":"T. Lee , F. Qi , K. Peirce , J. Natalwala , V. Chapple , P.J. Mark , K. Sanders , Y. Liu","doi":"10.1016/j.rbmo.2025.105080","DOIUrl":"10.1016/j.rbmo.2025.105080","url":null,"abstract":"<div><div>Unlike embryos that display two pronuclei (2PN), monopronucleated (1PN) embryos are assumed to be haploid and can be routinely discarded. Although there are reports of live births after 1PN embryo transfer, the developmental and clinical prognosis of 1PN embryos has not been systematically evaluated. The aim of this review was to elucidate the developmental, clinical and neonatal outcomes of 1PN embryos compared with 2PN embryos. Twenty-four studies met the inclusion criteria. The blastulation rate was lower in 1PN embryos compared with 2PN embryos [risk ratio (RR) 0.50, 95% CI 0.48–0.51]. The live birth rate was lower in 1PN blastocysts when untested (RR 0.81, 95% CI 0.72–0.90), but was similar after euploidy confirmation by preimplantation genetic testing for aneuploidy (RR 0.85, 95% CI 0.59–1.23). The euploidy rate was comparable in 1PN and 2PN embryos (RR 0.91, 95% CI 0.81–1.02). In a subgroup analysis of untested embryos, 1PN-intracytoplasmic sperm injection (ICSI) blastocysts had a lower live birth rate compared with 2PN-ICSI blastocysts (RR 0.26, 95% CI 0.13–0.50), while no difference was observed with IVF (RR 0.93, 95% CI 0.82–1.06). These results are particularly important for patients with a poor prognosis and limited 2PN embryos, and can aid reproductive professionals to counsel patients on the clinical use of 1PN embryos. Future studies should utilise time-lapse and preimplantation genetic testing technologies for confirmation of diploidy and biparental inheritance. Monopronucleated embryos can be viable, expanding options beyond 2PN embryos.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 2","pages":"Article 105080"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Can a non-invasive approach predicting embryonic pregnancy potential be developed by analysing proteins in single blastocyst conditioned medium (SBCM)?
Design
Patients with infertility who underwent vitrified-warmed single blastocyst transfer (January 2021–December 2023) were included in this study. SBCM corresponding to transferred blastocysts was collected and analysed using highly sensitive single-molecule array technology to quantify the concentrations of 12 candidate proteins (n = 1390). Key proteins were selected for model development for prediction of clinical pregnancy using a training set (n = 240), and subsequently validated with a test set (n = 60). Performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curves.
Results
Among the 12 proteins examined, elevated concentrations of interleukin-8 (IL-8) (P < 0.001) and beta-human chorionic gonadotrophin (B-HCG) (P = 0.009) were associated with a significantly higher clinical pregnancy rate, whereas elevated C-C motif chemokine 5 (RANTES, ‘regulated on activation, normal T cell expressed and secreted’) was associated with a significantly lower pregnancy rate (P < 0.001). Individual biomarkers demonstrated modest discriminatory capacity for predicting clinical pregnancy for IL-8 (AUC = 0.600; P = 0.03), B-HCG (AUC = 0.588; P = 0.002) and RANTES (AUC = 0.397; P = 0.001). A multi-protein prediction model integrating these three biomarkers exhibited superior discriminatory performance (AUC = 0.722), and significantly outperformed each individual protein marker (P ≤ 0.005). The combined model incorporating both the multi-protein signature and morphological grading parameters achieved optimal predictive accuracy (AUC = 0.744). These findings were validated in an independent test set (AUC = 0.724).
Conclusions
This study establishes a novel multi-protein model for predicting clinical pregnancy. The combination of IL-8, B-HCG and RANTES in SBCM provides a promising non-invasive approach for embryo selection, particularly when integrated with morphological assessment.
{"title":"Beyond morphology: a multi-protein analysis of single blastocyst conditioned medium to predict pregnancy potential of embryos","authors":"Peilin Chen , Chunyu Huang , Hongzhan Zhang , Huixian Zhong, Feng Xiong, Zhiqiang Liu, Yong Zeng, Qing Sun, Lianghui Diao","doi":"10.1016/j.rbmo.2025.105213","DOIUrl":"10.1016/j.rbmo.2025.105213","url":null,"abstract":"<div><h3>Research question</h3><div>Can a non-invasive approach predicting embryonic pregnancy potential be developed by analysing proteins in single blastocyst conditioned medium (SBCM)?</div></div><div><h3>Design</h3><div>Patients with infertility who underwent vitrified-warmed single blastocyst transfer (January 2021–December 2023) were included in this study. SBCM corresponding to transferred blastocysts was collected and analysed using highly sensitive single-molecule array technology to quantify the concentrations of 12 candidate proteins (<em>n</em> = 1390). Key proteins were selected for model development for prediction of clinical pregnancy using a training set (<em>n</em> = 240), and subsequently validated with a test set (<em>n</em> = 60). Performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curves.</div></div><div><h3>Results</h3><div>Among the 12 proteins examined, elevated concentrations of interleukin-8 (IL-8) (<em>P</em> < 0.001) and beta-human chorionic gonadotrophin (B-HCG) (<em>P</em> = 0.009) were associated with a significantly higher clinical pregnancy rate, whereas elevated C-C motif chemokine 5 (RANTES, ‘regulated on activation, normal T cell expressed and secreted’) was associated with a significantly lower pregnancy rate (<em>P</em> < 0.001). Individual biomarkers demonstrated modest discriminatory capacity for predicting clinical pregnancy for IL-8 (AUC = 0.600; <em>P</em> = 0.03), B-HCG (AUC = 0.588; <em>P</em> = 0.002) and RANTES (AUC = 0.397; <em>P</em> = 0.001). A multi-protein prediction model integrating these three biomarkers exhibited superior discriminatory performance (AUC = 0.722), and significantly outperformed each individual protein marker (<em>P</em> ≤ 0.005). The combined model incorporating both the multi-protein signature and morphological grading parameters achieved optimal predictive accuracy (AUC = 0.744). These findings were validated in an independent test set (AUC = 0.724).</div></div><div><h3>Conclusions</h3><div>This study establishes a novel multi-protein model for predicting clinical pregnancy. The combination of IL-8, B-HCG and RANTES in SBCM provides a promising non-invasive approach for embryo selection, particularly when integrated with morphological assessment.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 2","pages":"Article 105213"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145842277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-08-11DOI: 10.1016/j.rbmo.2025.105206
Georg Griesinger , Qian Wang , Elena Labarta , Rose Li , Somjate Manipalviratn , Kshitiz Murdia , Emre Pabuccu , Elke Kahler
The route of administration significantly influences the pharmacokinetics of progestogens. For luteal phase support (LPS) after fresh embryo transfer in IVF, ESHRE recommends vaginal, intramuscular, subcutaneous progesterone or oral dydrogesterone. This network meta-analysis evaluated the relative effectiveness of progestogen administration routes on clinical pregnancy rate (CPR) and live birth rate (LBR) in fresh IVF cycles. A systematic review identified peer-reviewed, published randomized controlled trials (RCTs) comparing individual progestogens (versus placebo or other progestogens) and reporting CPR. Studies involving frozen–thawed transfers, non-progestogenic LPS or non-available formulations were excluded. Of the 24 RCTs included, oral administration was the only route reaching statistical significance for increased CPR, although overlapping confidence intervals across comparisons indicate uncertainty in clinically relevant superiority. For LBR, only oral and intramuscular routes demonstrated statistically significant improvement versus placebo; vaginal and subcutaneous did not. These findings, supported by sensitivity analyses excluding low-quality and older studies, suggest that oral and intramuscular progestogens may be more effective in improving IVF outcomes, but outcome differences require further studies. This study substantially advances the evidence base by integrating recent data, applying rigorous quality assessment standards and using state-of-the-art network meta-analytic methodology, contributing to refining recommendations for optimal progestogenic LPS in fresh IVF cycles.
{"title":"Network meta-analysis of progestogen administration routes for luteal phase support in fresh embryo transfer IVF cycles","authors":"Georg Griesinger , Qian Wang , Elena Labarta , Rose Li , Somjate Manipalviratn , Kshitiz Murdia , Emre Pabuccu , Elke Kahler","doi":"10.1016/j.rbmo.2025.105206","DOIUrl":"10.1016/j.rbmo.2025.105206","url":null,"abstract":"<div><div>The route of administration significantly influences the pharmacokinetics of progestogens. For luteal phase support (LPS) after fresh embryo transfer in IVF, ESHRE recommends vaginal, intramuscular, subcutaneous progesterone or oral dydrogesterone. This network meta-analysis evaluated the relative effectiveness of progestogen administration routes on clinical pregnancy rate (CPR) and live birth rate (LBR) in fresh IVF cycles. A systematic review identified peer-reviewed, published randomized controlled trials (RCTs) comparing individual progestogens (versus placebo or other progestogens) and reporting CPR. Studies involving frozen–thawed transfers, non-progestogenic LPS or non-available formulations were excluded. Of the 24 RCTs included, oral administration was the only route reaching statistical significance for increased CPR, although overlapping confidence intervals across comparisons indicate uncertainty in clinically relevant superiority. For LBR, only oral and intramuscular routes demonstrated statistically significant improvement versus placebo; vaginal and subcutaneous did not. These findings, supported by sensitivity analyses excluding low-quality and older studies, suggest that oral and intramuscular progestogens may be more effective in improving IVF outcomes, but outcome differences require further studies. This study substantially advances the evidence base by integrating recent data, applying rigorous quality assessment standards and using state-of-the-art network meta-analytic methodology, contributing to refining recommendations for optimal progestogenic LPS in fresh IVF cycles.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 2","pages":"Article 105206"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-07-29DOI: 10.1016/j.rbmo.2025.105178
Gaetano Riemma , Juan Antonio García-Velasco , Mauricio S. Abrão , Umberto Leone Roberti Maggiore , Michele Vignali , Eugenio Solima , Marcello Ceccaroni , Vito Chiantera , Gaby N. Moawad , Antonio Simone Laganà , Vittorio Agrifoglio , Pasquale De Franciscis , Mariano Catello Di Donna , Antonio D’Amato , Alessandro Favilli , Andrea Etrusco
This systematic review and meta-analysis (CRD42024588171) compared the effectiveness of surgery followed by IVF/intracytoplasmic sperm injection (IVF/ICSI) with direct IVF/ICSI (i.e. without previous surgery) on the reproductive outcomes of infertile women with ovarian endometriomas (OMA) and deep infiltrating endometriosis (DIE), analysing 22 studies with 3590 participants. Surgery followed by IVF/ICSI did not improve the live birth rate significantly in patients with OMA (OR 0.89, 95% CI 0.68–1.16) or DIE (OR 1.82, 95% CI 0.70–4.77). The clinical pregnancy rate was also unaffected by surgery (OMA: OR 1.13, 95% CI 0.80–1.59; DIE: OR 1.28, 95% CI 0.71–2.31). The pregnancy loss rate remained comparable between the surgical and non-surgical groups. In the OMA subgroup, surgery reduced the concentration of anti-Müllerian hormone (mean difference -0.57, 95% CI -1.02 to -0.12) and number of retrieved oocytes (mean difference -1.24, 95% CI -1.70 to -0.77) significantly. These findings highlight the importance of careful consideration of the ovarian reserve when opting for surgical intervention. Consequently, IVF/ICSI should be prioritized as the initial treatment for infertility in patients with endometriosis, reserving surgery for symptom management, patient-specific factors, or clearly defined clinical indications to optimize reproductive outcomes and patient safety. However, the very low certainty of evidence, the available study designs, and their inherent limitations warrant caution when interpreting such findings.
本系统回顾和荟萃分析（CRD42024588171）比较了手术后体外受精/胞浆内单精子注射（IVF/ICSI）与直接体外受精/ICSI（即没有手术）对患有卵巢子宫内膜异位症（OMA）和深浸润性子宫内膜异位症（DIE）的不孕妇女的生殖结果的有效性，分析了22项研究，共3590名参与者。手术后IVF/ICSI并没有显著提高OMA患者的活产率（OR 0.89, 95% CI 0.68-1.16）或死亡（OR 1.82, 95% CI 0.70-4.77）。临床妊娠率也不受手术影响（OMA: OR 1.13, 95% CI 0.80-1.59；死亡：OR 1.28, 95% CI 0.71-2.31）。手术组和非手术组的妊娠失败率保持相当。在OMA亚组中，手术显著降低了抗勒氏激素浓度（平均差异为-0.57,95% CI为-1.02 ~ -0.12）和卵母细胞数量（平均差异为-1.24,95% CI为-1.70 ~ -0.77）。这些发现强调了在选择手术干预时仔细考虑卵巢储备的重要性。因此，IVF/ICSI应优先作为子宫内膜异位症患者不孕症的初始治疗，保留手术治疗症状、患者特异性因素或明确定义的临床适应症，以优化生殖结果和患者安全。然而，证据的极低确定性，现有的研究设计及其固有的局限性，在解释这些发现时需要谨慎。
{"title":"IVF/ICSI or surgery as first approach for the treatment of infertility associated with ovarian and deep infiltrating endometriosis? A systematic review and meta-analysis","authors":"Gaetano Riemma , Juan Antonio García-Velasco , Mauricio S. Abrão , Umberto Leone Roberti Maggiore , Michele Vignali , Eugenio Solima , Marcello Ceccaroni , Vito Chiantera , Gaby N. Moawad , Antonio Simone Laganà , Vittorio Agrifoglio , Pasquale De Franciscis , Mariano Catello Di Donna , Antonio D’Amato , Alessandro Favilli , Andrea Etrusco","doi":"10.1016/j.rbmo.2025.105178","DOIUrl":"10.1016/j.rbmo.2025.105178","url":null,"abstract":"<div><div>This systematic review and meta-analysis (CRD42024588171) compared the effectiveness of surgery followed by IVF/intracytoplasmic sperm injection (IVF/ICSI) with direct IVF/ICSI (i.e. without previous surgery) on the reproductive outcomes of infertile women with ovarian endometriomas (OMA) and deep infiltrating endometriosis (DIE), analysing 22 studies with 3590 participants. Surgery followed by IVF/ICSI did not improve the live birth rate significantly in patients with OMA (OR 0.89, 95% CI 0.68–1.16) or DIE (OR 1.82, 95% CI 0.70–4.77). The clinical pregnancy rate was also unaffected by surgery (OMA: OR 1.13, 95% CI 0.80–1.59; DIE: OR 1.28, 95% CI 0.71–2.31). The pregnancy loss rate remained comparable between the surgical and non-surgical groups. In the OMA subgroup, surgery reduced the concentration of anti-Müllerian hormone (mean difference -0.57, 95% CI -1.02 to -0.12) and number of retrieved oocytes (mean difference -1.24, 95% CI -1.70 to -0.77) significantly. These findings highlight the importance of careful consideration of the ovarian reserve when opting for surgical intervention. Consequently, IVF/ICSI should be prioritized as the initial treatment for infertility in patients with endometriosis, reserving surgery for symptom management, patient-specific factors, or clearly defined clinical indications to optimize reproductive outcomes and patient safety. However, the very low certainty of evidence, the available study designs, and their inherent limitations warrant caution when interpreting such findings.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 2","pages":"Article 105178"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Does maternal history of unexplained recurrent pregnancy loss (RPL) increase the risk for adverse neonatal outcomes after assisted reproductive technology (ART)?
Design
Embryo transfer cycles with singleton live births (n = 37,703) were included from three fertility centres between 2014 and 2021. Infertile patients were divided into three groups according to their pregnancy loss history: two or more; one; and none (control group). A range of neonatal outcomes were followed up by telephone interviews using standardized questionnaires. Multivariate logistic regression analysis was used to control for potential confounders, and subgroup analyses were conducted for primary and secondary RPL.
Results
A total of 925 patients experienced RPL (one pregnancy loss n = 3466; no pregnancy losses after exclusion n = 33312). Compared with the patients without pregnancy loss, the RPL group had significantly higher risks of preterm birth (adjusted odds ratio [aOR] 1.25, 95% CI 1.01 to 1.56) and low birth weight (aOR 1.32, 95% CI 1.00 to 1.74). No significant associations were observed between RPL and other neonatal outcomes. Patients who had experienced only one loss had no increased risk of adverse neonatal outcomes versus those without losses. In subgroup analyses, no differences in neonatal outcomes were observed between the primary and secondary RPL.
Conclusions
Among infertile patients undergoing ART, a history of unexplained RPL was associated with an increased risk of preterm birth and low birth weight in neonates. Absolute risk increments were small, and the clinical significance of these findings should be interpreted with caution.
研究问题：产妇不明原因复发性妊娠丢失（RPL）史是否会增加辅助生殖技术（ART）后新生儿不良结局的风险？设计纳入2014年至2021年间三个生育中心的单胎活产的胚胎移植周期（n = 37,703）。不孕症患者按流产史分为三组：两次及以上；一个;没有（对照组）。通过使用标准化问卷的电话访谈跟踪了一系列新生儿结局。采用多因素logistic回归分析控制潜在混杂因素，并对原发性和继发性RPL进行亚组分析。结果共925例患者发生RPL，其中1例妊娠丢失 = 3466，排除后无妊娠丢失 = 33312。与未流产的患者相比，RPL组早产（调整优势比[aOR] 1.25, 95% CI 1.01 ~ 1.56）和低出生体重（aOR 1.32, 95% CI 1.00 ~ 1.74）的风险显著升高。在RPL和其他新生儿结局之间没有观察到显著的关联。只经历过一次损失的患者与没有损失的患者相比，不良新生儿结局的风险没有增加。在亚组分析中，在原发性和继发性RPL之间没有观察到新生儿结局的差异。结论在接受抗逆转录病毒治疗的不孕症患者中，不明原因RPL病史与新生儿早产和低出生体重的风险增加有关。绝对风险增量很小，这些发现的临床意义应谨慎解释。
{"title":"Association between unexplained recurrent pregnancy loss history and adverse neonatal outcomes among infertile women undergoing ART","authors":"Genbao Xing , Xingyu Miao , Leizhen Xia , Jiaying Lin , Jing Zhu , Lifeng Tian , Yan Zhao , Jialyu Huang","doi":"10.1016/j.rbmo.2025.105243","DOIUrl":"10.1016/j.rbmo.2025.105243","url":null,"abstract":"<div><h3>Research question</h3><div>Does maternal history of unexplained recurrent pregnancy loss (RPL) increase the risk for adverse neonatal outcomes after assisted reproductive technology (ART)?</div></div><div><h3>Design</h3><div>Embryo transfer cycles with singleton live births (<em>n</em> = 37,703) were included from three fertility centres between 2014 and 2021. Infertile patients were divided into three groups according to their pregnancy loss history: two or more; one; and none (control group). A range of neonatal outcomes were followed up by telephone interviews using standardized questionnaires. Multivariate logistic regression analysis was used to control for potential confounders, and subgroup analyses were conducted for primary and secondary RPL.</div></div><div><h3>Results</h3><div>A total of 925 patients experienced RPL (one pregnancy loss <em>n</em> = 3466; no pregnancy losses after exclusion <em>n</em> = 33312). Compared with the patients without pregnancy loss, the RPL group had significantly higher risks of preterm birth (adjusted odds ratio [aOR] 1.25, 95% CI 1.01 to 1.56) and low birth weight (aOR 1.32, 95% CI 1.00 to 1.74). No significant associations were observed between RPL and other neonatal outcomes. Patients who had experienced only one loss had no increased risk of adverse neonatal outcomes versus those without losses. In subgroup analyses, no differences in neonatal outcomes were observed between the primary and secondary RPL.</div></div><div><h3>Conclusions</h3><div>Among infertile patients undergoing ART, a history of unexplained RPL was associated with an increased risk of preterm birth and low birth weight in neonates. Absolute risk increments were small, and the clinical significance of these findings should be interpreted with caution.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 2","pages":"Article 105243"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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