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Reproductive Biomedicine Online[JOURNAL]

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Quantitative characterization of uterine peristalsis propagation throughout the menstrual cycle using a novel intracavitary electrohysterography method.

Imaz-Higuera J, Garcia-Casado J, Mira-Tomas JM … +7 more , Diaz-Martinez A, Faubel PA, Sanz SC, Cortés GC, de Arriba-Garcia M, Aparicio JL, Alberola-Rubio J

Reprod Biomed Online · 2026 Apr · PMID 41722479 · Publisher ↗

RESEARCH QUESTION: What are the characteristic propagation patterns of uterine contractions during the menstrual cycle in fertile women as assessed by intracavitary electrohysterography (IC-EHG). DESIGN: A prospective, m... RESEARCH QUESTION: What are the characteristic propagation patterns of uterine contractions during the menstrual cycle in fertile women as assessed by intracavitary electrohysterography (IC-EHG). DESIGN: A prospective, multicentre cohort study was conducted at IVI clinics in Madrid, Barcelona and Valencia (Spain). The frequencies of occurrence of propagations (wavefront/min), their direction (cervix to fundus [C2F], fundus to cervix [F2C], opposing or random) and their velocity were measured. Features were extracted from 30 min IC-EHG recordings performed during the mid-follicular, early luteal and late luteal phases. Forty-three women were enrolled, and 113 recordings were suitable for inclusion in the analysis. Participants were aged 18-39 years and had proven fertility, regular menstrual cycles and a body mass index of 18.5-27.0 kg/m². Exclusion criteria comprised pregnancy, recent intercourse or hysteroscopy, uterine abnormalities, hormonal treatments and other relevant gynaecological conditions. RESULTS: Approximately two-thirds of the contractions detected by IC-EHG belonged to propagated wavefronts, while the remaining one-third were non-propagated (local) contractions. The highest frequency of propagated events was observed in the early luteal phase. The uterine peristalsis exhibited transient short-term clusters of wavefronts with the same propagation direction that shifted over time. F2C waves prevailed in the mid-follicular phase, C2F in the early luteal phase, and bidirectional activity in the late luteal phase. C2F wavefront propagation velocity was similar to that of F2C, which was higher in the mid-follicular phase than the late luteal phase. CONCLUSIONS: IC-EHG allows an objective assessment of uterine contraction propagation. The uterus manifested phase-dependent peristaltic propagation patterns in accordance with its specific physiological function. Short recordings (3-5 min) can bias the assessments of propagation patterns.

Effect of abnormal semen parameters on ICSI: morphokinetics and cumulative clinical outcomes of 10,623 embryos.

Quintana-Vehí A, Miguel-Escalada I, Pujol A … +6 more , Zamora MJ, Oliver M, Petrolo M, Dal Canto M, Rodríguez-Aranda A, Popovic M

Reprod Biomed Online · 2026 Apr · PMID 41720045 · Publisher ↗

RESEARCH QUESTION: Does sperm quality influence embryo morphokinetics, embryo quality and reproductive outcomes in intracytoplasmic sperm injection (ICSI) cycles? DESIGN: Retrospective cohort study (10,623 embryos from 1... RESEARCH QUESTION: Does sperm quality influence embryo morphokinetics, embryo quality and reproductive outcomes in intracytoplasmic sperm injection (ICSI) cycles? DESIGN: Retrospective cohort study (10,623 embryos from 1680 patients; 1836 ICSI cycles) conducted at a single IVF centre (2019-2023). Embryos were grouped by semen quality and origin: normozoospermia (n = 8799), severe oligozoospermia (n = 567), severe oligoasthenozoospermia (n = 716) and testicular sperm extraction (TESE) (n = 541). Time-lapse microscopy was used to assess morphokinetic parameters. Developmental and clinical outcomes were analysed for first and cumulative transfers. RESULTS: A total of 14,568 oocytes were inseminated. Normal fertilization (two pronuclei) was highest in the normozoospermia group (74.6%) and declined progressively with impaired semen quality: oligozoospermia (69.4%), oligoasthenzooospermia (68.3%) and TESE group (59.6%) (all P ≤ 0.042 versus normozoospermia). Correspondingly, the proportion of non-fertilized oocytes increased as follows: normozoospermia (9.8%), oligozoospermia (15.7%), oligoasthenozoospermia (15.8%) and TESE (22.1%) (all P ≤ 0.012 versus normozoospermia). One-pronucleus zygotes were also more frequent in the TESE group (7.2%) compared with the normozoospermia group (4.8%) (P = 0.019). The TESE-derived embryos showed accelerated cleavage from pronuclear fading to the five-cell stage (P ≤ 0.027). Blastocyst quality was reduced in the TESE and severe oligoasthenozoospermia groups. First transfer outcomes were comparable across groups; cumulative implantation, pregnancy and live birth rates per embryo transferred were lower for TESE (P ≤ 0.031). CONCLUSIONS: Semen origin significantly affects embryo development and cumulative outcomes in ICSI cycles. Although moderate impairments had limited effect, TESE-derived spermatozoa were associated with altered morphokinetics, poorer embryo quality and lower cumulative success rates. Sperm origin represents a clinically relevant factor for embryo evaluation and transfer decision-making.

Rethinking insemination for good-prognosis couples: the emotional and ethical burden of cryopreserved embryos never transferred.

Lawrenz B, Ata B

Reprod Biomed Online · 2026 Apr · PMID 41720044 · Publisher ↗

The cumulative live birth rate in assisted reproductive technology is directly proportional to oocyte yield; therefore, ovarian stimulation seeks to optimize the oocyte yield from treatment. Despite the inevitable attrit... The cumulative live birth rate in assisted reproductive technology is directly proportional to oocyte yield; therefore, ovarian stimulation seeks to optimize the oocyte yield from treatment. Despite the inevitable attrition during the culture, some couples may encounter an excess of embryos, resulting in the dilemma of how to manage their surplus embryos. The fate of surplus and unneeded embryos is contingent upon the legal framework and couples' preferences. A paradigm shift from surplus embryo cryopreservation to surplus oocyte cryopreservation prior to insemination may address these concerns. The availability of euploid blastocysts serves as the nearest surrogate marker for the likelihood of a live birth in subsequent embryo transfers, and current predictive models can calculate the average number of oocytes required to obtain one or more euploid blastocysts based on female age. Given the challenges of customizing ovarian stimulation to yield a precise number of oocytes, limiting oocyte insemination and cryopreserving the surplus oocytes may effectively prevent the creation of unwanted embryos. This 'smart insemination - preserving the rest' strategy will not eliminate the need for gamete storage; nonetheless, it may reduce the number of possibly unwanted embryos stored and address the complex issue of their management.

Evaluation of a web-based decision aid for couples at risk of transmitting a genetic disease: a randomized controlled trial.

Engbersen-Severijns Y, de Die-Smulders CEM, Bijlsma EK … +13 more , Corsten-Janssen N, Houwink EJF, Joosten SJR, van Kuijk SMJ, Lichtenbelt KD, Ottenheim CPE, Scheepers HCJ, Stuurman KE, Tan-Sindhunata MB, Van Vliet-Lachotzki EH, de Vries H, van der Weijden GDEM, van Osch LADM

Reprod Biomed Online · 2026 Apr · PMID 41720043 · Publisher ↗

RESEARCH QUESTION: What are the immediate and sustained effects of the decision aid on key elements of informed decision-making (decisional conflict, knowledge, realistic expectations and deliberation) among couples at r... RESEARCH QUESTION: What are the immediate and sustained effects of the decision aid on key elements of informed decision-making (decisional conflict, knowledge, realistic expectations and deliberation) among couples at risk of transmitting a genetic disease to their offspring in a multi-centre randomized controlled trial (RCT)? DESIGN: Effects were assessed with individual questionnaires in a multicentre RCT. The intervention group (n = 98) received access to the decision aid, whereas the (active) control group (n = 106) accessed a standardized information page. Outcomes were measured before use (T0), immediately after use (T1), at 1 (T2) and 6 months (T3) after use of the decision aid or standardized information. RESULTS: Between-group analyses showed significant effects of the decision aid on the informed decisional conflict subscale (T1) but not on overall decisional conflict. Immediately after use (T1), participants in the intervention group scored significantly higher on preparation for decision-making and overall appreciation compared with the control group. Within-group analyses revealed that both the decision aid and the standardized information page decreased decisional conflict and increased knowledge and realistic expectations, across all time points (T1-T3). For the control group, deliberation significantly improved at T1, T2 and T3, whereas, for the intervention group, significant improvements were observed only at T2 and T3. CONCLUSION: The decision aid outperforms the standardized information page in preparation for decision-making and overall appreciation. Future research should explore how to improve tailoring of information tools to individual characteristics and identify which couples benefit most from concise versus comprehensive information at different decision-making stages.

Comparison of one-step and conventional warming in sibling donor oocytes: a proof-of-concept study.

Cobo A, Coello A, Murria L … +4 more , Garijo Y, José de Los Santos M, García-Velasco JA, Bronet F

Reprod Biomed Online · 2026 Mar · PMID 41719956 · Publisher ↗

RESEARCH QUESTION: Are there differences in survival, embryo development and clinical outcomes between sibling oocytes warmed using one-step and conventional protocols? DESIGN: A prospective, randomized, proof-of-concept... RESEARCH QUESTION: Are there differences in survival, embryo development and clinical outcomes between sibling oocytes warmed using one-step and conventional protocols? DESIGN: A prospective, randomized, proof-of-concept trial using sibling donor oocytes to evaluate a one-step warming procedure. A total of 352 metaphase II oocytes (n = 30 donors) that had been previously vitrified using the conventional procedure were included. Just before warming, the oocytes were randomized into two groups: one-step warming (n = 179) and conventional warming (n = 173). The conventional warming protocol takes 10 min and involves three steps, using decreasing concentrations of trehalose. One-step warming only requires 1 min in 1.0 M trehalose solution. The main outcome was the survival rate. Fertilization rates, embryo quality, clinical results and oocyte developmental competence were also analysed. RESULTS: The survival rate was 96.1% in the one-step warming group and 94.2% in the conventional-warming group, with no statistically significant difference. No differences were found when comparing the usable blastocyst rate (55.3% versus 52.1%) or good-quality blastocyst rate (46.1% versus 43.6%) of the one-step and conventional warming protocols, respectively. Similarly, no significant differences were found between implantation rates (69.2% versus 58.8%, respectively) and ongoing pregnancy rate per embryo transfer (53.8% versus 41.2%). The logistic regression analysis showed that the warming protocol did not correlate with ongoing pregnancy rate. CONCLUSION: One-step warming can be safely applied to donor metaphase II oocytes, providing similar survival rates and clinical outcomes compared with conventional warming.

Quantitative analysis of uterine peristalsis in women with adenomyosis using optical flow for motion quantification.

Latif S, Saeed SU, Hu Y … +4 more , De Braud L, Yasmin E, Saridogan E, Mavrelos D

Reprod Biomed Online · 2026 Mar · PMID 41713072 · Publisher ↗

RESEARCH QUESTION: Do women with adenomyosis have altered uterine peristalsis, and can an objective and reproducible tool be developed to quantify uterine peristalsis on transvaginal sonography (TVS)? DESIGN: Prospective... RESEARCH QUESTION: Do women with adenomyosis have altered uterine peristalsis, and can an objective and reproducible tool be developed to quantify uterine peristalsis on transvaginal sonography (TVS)? DESIGN: Prospective observational cohort study in women with moderate to severe adenomyosis (n = 26) or a normal uterus (n = 40) undergoing TVS during assisted conception. TVS recordings (n = 143) were conducted at baseline, day 6-10 of ovarian stimulation and day of embryo transfer by operator A, and then repeated by operator A, B or C. Image data were stored offline for optical flow analysis. Pixel-level displacements for points at the endometrial--myometrial junction were used to compute peristalsis frequency and amplitude by fitting to the two-dimensional wave equation. Fit error was taken as a measure of wave coordination. Inter-class correlation coefficient (ICC) was calculated to assess inter- and intra-observer agreement. RESULTS: Women with adenomyosis had a significantly higher fit error at all time points during the IVF cycle (baseline: + 0.725, P < 0.001; ovarian stimulation: + 0.612, P = 0.004; embryo transfer: + 0.627, P < 0.001), indicating lower uterine peristalsis coordination compared with women with a normal uterus. Inter- and intra-observer agreement for each wave feature (frequency, amplitude and coordination of uterine peristalsis and myometrial contractility) was found to be moderate to good (intra-observer ICC: 0.62-0.75, inter-observer ICC: 0.58-0.79). CONCLUSION: An objective and reproducible measuring tool is proposed to quantify uterine peristalsis using TVS, with potential for wide application across assisted conception and gynaecology settings.

Double embryo transfer with mosaic embryos: experience from a large academic fertility centre.

Kelly AG, McFarland Z, Besser A … +2 more , Grifo JA, Blakemore JK

Reprod Biomed Online · 2026 Mar · PMID 41713071 · Publisher ↗

RESEARCH QUESTION: What are the overall, singleton and twin live birth rates (LBR) after a double embryo transfer (DET) involving mosaic embryos? DESIGN: This was a retrospective cohort study of DET with at least one mos... RESEARCH QUESTION: What are the overall, singleton and twin live birth rates (LBR) after a double embryo transfer (DET) involving mosaic embryos? DESIGN: This was a retrospective cohort study of DET with at least one mosaic embryo between 1 December 2016 and 1 December 2024. Each DET was assigned a prognostic score (A-F) based on the ploidy of both embryos. The primary outcome was the overall, singleton and twin LBR of good-prognosis (A and B), moderate-prognosis (C and D) and poor-prognosis (E and F) DET. Secondary outcomes were the LBR for mosaic/mosaic compared with euploid/mosaic transfers. Comparisons were also made with previously published data on euploid/euploid transfers. RESULTS: In total, there were 38 DET: 22 mosaic/mosaic and 16 euploid/mosaic. Twenty-nine (76.3%) patients had prior failed euploid transfers, and 19 (86.4%) mosaic/mosaic patients did not have any euploid embryos. The differences in overall LBR between the prognostic groups did not reach significance [65.0% (13/20) good-prognosis group versus 71.4% (5/7) moderate-prognosis group versus 45.5% (5/11) poor-prognosis group; P = 0.5]. The twin LBR was higher in the good-prognosis group (46.2%) compared with the moderate- and poor-prognosis groups (0% for both; P = 0.04). Overall [72.7% (16/22) versus 43.8% (7/16); P = 0.07], singleton [54.5% (12/22) versus 31.3% (5/11); P = 0.20] and twin [18.2% (4/22) versus 12.5% (2/16); P = 0.6] LBR were similar between mosaic/mosaic and euploid/mosaic DET. While the multiple LBR was high in both groups, it was lower for mosaic/mosaic and euploid/mosaic DET compared with euploid/euploid DET [26.1% (6/23) versus 49.8% (113/227, previously published data); P = 0.04]. CONCLUSIONS: Caution must be exercised with mosaic embryos as they can behave like euploid embryos, and DET can result in twins. DET with moderate- or poor-prognosis mosaic embryos had lower twin rates and may be reasonably considered. Larger studies are needed.

Parenthood intentions and fertility knowledge in the Nordic population 1970 to 2021 - a scoping review.

Lakjuni SÁ, Schmidt L, Ziebe S … +3 more , Sylvest R, Vassard D, Hviid Malling GM

Reprod Biomed Online · 2026 Mar · PMID 41702275 · Publisher ↗

Fertility rates are decreasing globally, and the Nordic countries currently have fertility rates of 1.3-1.5 per woman. The objectives of this scoping review, covering the Nordic welfare states since 1970, were to explore... Fertility rates are decreasing globally, and the Nordic countries currently have fertility rates of 1.3-1.5 per woman. The objectives of this scoping review, covering the Nordic welfare states since 1970, were to explore women's and men's parenthood intentions, their assessment of important circumstances for family building and their fertility knowledge. Overall, 24 quantitative studies and 6 qualitative studies were included. Across studies, the majority of both women and men expressed a desire to have children, while 0-14% did not wish to do so. Among those having parenthood intentions approximately 85% wanted to have two or three children. Parenthood intentions did not decline during the 50-year period of the empirical studies. Hence, as fertility rates are substantially decreasing, the gap between parenthood intentions and actual birth rates is widening. Since 2006, 12 of the included studies explored study participants' fertility knowledge. All studies except one reported uncertain fertility knowledge, either overestimating or underestimating the probability of spontaneous pregnancy, or overestimating the success rate after IVF treatment. There is an urgent need for cross-disciplinary and structural efforts to bridge the increasing gap between desired and actualized parenthood.

Oocyte quality in women with diminished ovarian reserve: not as poor as assumed.

Yan EQ, Chen HX, Li YL … +2 more , Jin L, Ma BX

Reprod Biomed Online · 2026 Mar · PMID 41702274 · Publisher ↗

RESEARCH QUESTION: How does diminished ovarian reserve (DOR) affect euploid blastocyst rates, and how many embryos need to be biopsied for women with or without DOR to achieve one euploid embryo? DESIGN: A retrospective... RESEARCH QUESTION: How does diminished ovarian reserve (DOR) affect euploid blastocyst rates, and how many embryos need to be biopsied for women with or without DOR to achieve one euploid embryo? DESIGN: A retrospective study was conducted at a single reproductive centre, involving 694 women (126 with and 568 without DOR) undergoing 803 preimplantation genetic testing for aneuploidies (PGT-A) cycles from 2016 to 2024. DOR was defined as a concentration of anti-Müllerian hormone below 1.1 ng/ml and/or an antral follicle count of less than 7. Participants were stratified by age into three groups: <35, 35-39 and >39 years. Euploidy rates and pregnancy outcomes were compared between the DOR and non-DOR groups. Cumulative euploid embryo acquisition was analysed. RESULTS: DOR patients showed comparable euploidy rates to their non-DOR counterparts. The number of embryos required to obtain a euploid embryo was a: for age <35 years, a mean of 1.6 embryos for the DOR group and 1.7 for the non-DOR group; for age 35-39 years, a mean of 1.9 and 2.3 embryos, respectively; and for age >39 years, a mean of 7.2 and 4.2 embryos, respectively. In women over aged 39 years, the mean number of euploid embryos obtained remained low even after two retrievals for both groups. Pregnancy outcomes after euploid embryo transfer were similar between the two groups. CONCLUSIONS: Participants with DOR had similar euploidy rates and pregnancy outcomes to non-DOR patients. Limited embryo quantity, rather than inferior oocyte quality, thus remains the predominant challenge for individuals with DOR.

Day 3 versus Day 5 refreshment of single-step medium for embryos cultured in a benchtop dry incubator: a randomized sibling oocyte study.

Elkhatib I, Bayram A, Abdala A … +6 more , Hourani N, Ferracuti V, Siqueira S, Kalafat E, Fatemi HM, Nogueira D

Reprod Biomed Online · 2026 Mar · PMID 41702273 · Publisher ↗

RESEARCH QUESTION: Does refreshment of single-step culture medium on Day 3 impact blastocyst formation and ploidy rates in embryos cultured in benchtop dry incubators? DESIGN: This randomized sibling oocyte study was per... RESEARCH QUESTION: Does refreshment of single-step culture medium on Day 3 impact blastocyst formation and ploidy rates in embryos cultured in benchtop dry incubators? DESIGN: This randomized sibling oocyte study was performed between July 2021 and October 2023 including 177 patients who underwent preimplantation genetic testing for aneuploidy (PGT-A). Following intracytoplasmic sperm injection, 3016 metaphase II (MII) oocytes were randomized equally to two culture conditions: (a) medium refreshment on Day 3 (R-D3) or (b) medium refreshment on Day 5 (R-D5). All embryos were cultured in single-step medium in a benchtop dry incubator. No embryo assessments were performed between fertilization check and Day 5. Post-insemination outcomes and ploidy rates were compared between the groups. RESULTS: Fertilization rates were similar between R-D3 and R-D5 (OR 0.89, 95% CI 0.75-1.07; P = 0.212). No significant differences in total usable blastocysts (OR 0.88, 95% CI 0.75-1.02; P = 0.091), euploid blastocysts (OR 0.95, 95% CI 0.80-1.13; P = 0.561) or mosaic blastocysts (OR 1.06, 95% CI 0.72-1.56; P = 0.771) per inseminated MII oocyte were observed. Similar results were observed per two pronuclei (2PN) embryo. However, R-D5 was associated with lower odds of Day 5 blastulation (OR 0.80, 95% CI 0.66-0.98; P = 0.032) and high-quality blastulation per inseminated MII oocyte (OR 0.82, 95% CI 0.68-0.98; P = 0.027), although this was not significant when analysed per 2PN embryo. Sensitivity analyses did not identify interactions between treatment group and cycle characteristics. CONCLUSION: Omitting the refreshment of single-step medium on Day 3 does not compromise the viability of euploid embryos to blastocyst stage, but does lead to a slight reduction in the number of morphologically high-quality blastocysts.

Epidemiology of endometriosis based on real-world data in Japan.

Ohashi M, Matsubayashi J, Sugeta K … +4 more , Yano Y, Kitaoka K, Murakami T, Tsuji S

Reprod Biomed Online · 2026 Apr · PMID 41692664 · Publisher ↗

RESEARCH QUESTION: Considering the progressively delayed age of pregnancy, what is the current epidemiology of endometriosis in Japan, including its prevalence, incidence and medication patterns, as revealed by a large-s... RESEARCH QUESTION: Considering the progressively delayed age of pregnancy, what is the current epidemiology of endometriosis in Japan, including its prevalence, incidence and medication patterns, as revealed by a large-scale, real-world dataset? DESIGN: A descriptive analysis of a health insurance dataset from January 2005 to July 2023. The study included adolescent girls and women aged 15 years or older with available data and at least 2 years of follow-up data. The main outcome measures were the prevalence of endometriosis, the age-specific incidence and the hypothetical cumulative incidences. RESULTS: Initially, 4,917,037 adolescent girls and women with at least 2 years of follow-up data were identified as potential participants, 285,309 of whom were diagnosed with endometriosis at 15-50 years of age. The prevalence of endometriosis increased consistently from 2006 to 2022, reaching 3.62% in 2022. The highest incidence was observed at 26 years of age. In older groups, the incidence of adenomyosis was higher than that of endometrioma. The hypothetical cumulative incidences were 37.34% for overall endometriosis and 20.08% for endometriosis treated with medications, with increasing trends observed for both conditions. CONCLUSIONS: The hypothetical lifetime incidence of endometriosis by age 50 years was approximately one-third among women, and one-fifth required medication for its treatment, highlighting the need for increased awareness and improved management in clinical settings.

Assessing the performance of generative AI chatbots in preimplantation genetic testing: a comparative study of expert evaluations.

Lledo B, Carbone P, Ortiz JA … +10 more , Morales R, Rodríguez-Arnedo A, Herrero L, Alvarez E, Ten J, Luque L, Castillo JC, Suñol J, Racca AL, Bernabeu A

Reprod Biomed Online · 2026 Mar · PMID 41690212 · Publisher ↗

RESEARCH QUESTION: How reliable are generative artificial intelligence (AI) chatbots in responding to patient-relevant questions about preimplantation genetic testing (PGT), as evaluated by reproductive medicine speciali... RESEARCH QUESTION: How reliable are generative artificial intelligence (AI) chatbots in responding to patient-relevant questions about preimplantation genetic testing (PGT), as evaluated by reproductive medicine specialists? DESIGN: A prospective evaluation was conducted comparing three publicly available generative AI models: ChatGPT-3.5, Gemini-1.5 and Llama-2. Twelve reproductive medicine specialists from different clinics assessed the chatbot-generated responses to 13 PGT-related questions, divided into simple and controversial categories. Each response was scored from 0 to 5 using predefined criteria. Assuming all answers were excellent, the maximum score was 25 points for simple questions and 40 points for controversial questions. RESULTS: In total, 156 evaluations were completed for each chatbot. Among the simple questions, 'What are the types and techniques used for PGT?' scored lowest (mean ± SD 2.83 ± 0.94). For the controversial questions, 'What is the percentage of aneuploidy that allows an embryo to be defined as mosaic?' scored lowest (mean ± SD 2.67 ± 1.22). ChatGPT performed best across both categories (simple 16.83 ± 1.80; controversial 27.75 ± 4.49), followed by Gemini (simple 14.92 ± 2.02; controversial 26.08 ± 3.99) and Llama (simple 13.58 ± 3.60; controversial 16.92 ± 4.96). Significant differences were observed, particularly between ChatGPT and Llama for both simple and controversial questions (P = 0.027 for simple, P < 0.001 for controversial), and between Gemini and Llama for controversial questions (P < 0.001). No significant performance differences were noted between participating specialists. CONCLUSIONS: Generative AI shows moderate reliability in addressing PGT-related enquiries, with ChatGPT and Gemini outperforming Llama. While performance was higher for simple questions than for controversial questions, the variability underscores the need for clinical oversight. Further refinement and validation are essential before widespread integration of AI tools in reproductive medicine.

Assessing the reproductive potential of late mature cryopreserved oocytes.

Bergin K, Mehra A, Slifkin R … +7 more , Baird M, Gounko D, Hernandez-Nieto C, Lee J, Canon C, Copperman AB, Sekhon L

Reprod Biomed Online · 2026 Mar · PMID 41690211 · Publisher ↗

RESEARCH QUESTION: Are there any differences in the warming, fertilization and embryo development outcomes of late mature cryopreserved oocytes versus immediately mature cryopreserved oocytes? DESIGN: This retrospective... RESEARCH QUESTION: Are there any differences in the warming, fertilization and embryo development outcomes of late mature cryopreserved oocytes versus immediately mature cryopreserved oocytes? DESIGN: This retrospective cohort study analysed autologous oocyte cryopreservation cycles with warming from January 2016 to September 2024. Group 1 comprised oocytes that were mature [metaphase II (MII)] at retrieval (assessed within 1 h of retrieval), and Group 2 comprised late mature oocytes, which included day 0 and day 1 late mature oocytes, which reached MII on re-assessment after short term (4-6 h) and next-day (18-28 h) rescue in-vitro maturation, respectively. Comparative statistics and univariate analysis were performed using Wilcoxon rank sum test and chi-squared test. Logistic regression fitted with a generalized estimating equation, adjusted for oocyte age, anti-Müllerian hormone, body mass index, year of oocyte cryopreservation and year of oocyte warming, was performed for warming survival, fertilization, blastulation and ploidy rates. RESULTS: Among 565 patients (699 cryopreservation and 629 warming cycles), Group 1 included 6899 oocytes that were mature at retrieval and Group 2 included 956 late mature oocytes. The warming survival rate was comparable between the groups (79.4% versus 78.0% for Groups 1 and 2, respectively; P = 0.33). The fertilization rate was significantly higher in Group 1 (75.3%) than Group 2 (59.8%) (adjusted OR 0.52, 95% CI 0.42-0.63; P < 0.001). Group 1 had significantly higher blastulation (37.7% versus 26.1%; P ≤ 0.001) and euploidy (54.5% versus 39.3%; P = 0.0023) rates compared with Group 2, and this was confirmed on adjusted analysis. A subanalysis showed no difference between day 0 and day 1 late mature oocytes. CONCLUSIONS: Late mature cryopreserved oocytes show lower reproductive potential than oocytes that are mature at retrieval. This could be attributed to dysynchronous cytoplasmic and nuclear maturation. Despite suboptimal development, late mature oocytes can create high-quality blastocysts, offering additional opportunities for future family-building.

Decoding uterine contractility: from physiology to pathology, through emerging technologies.

Nicolì P, Viganò P, de Ziegler D … +7 more , Saccone G, Saponara S, Vitale SG, Di Naro E, Cicinelli E, Pinto V, Vitagliano A

Reprod Biomed Online · 2026 Mar · PMID 41687169 · Publisher ↗

Uterine contractility has emerged as a potential key element in the orchestration of female reproductive functions, with specific motility patterns seemingly aligning with hormonal fluctuations throughout the menstrual c... Uterine contractility has emerged as a potential key element in the orchestration of female reproductive functions, with specific motility patterns seemingly aligning with hormonal fluctuations throughout the menstrual cycle. These dynamic contractility profiles appear to facilitate various stages of conception, underscoring the importance of maintaining physiological uterine kinetics for fertility. Altered uterine contractility might thus contribute to cases of unexplained infertility. By offering a comprehensive reappraisal of uterine contractility across both physiological and pathological contexts, this review has been undertaken to challenge conventional fertility paradigms. The review outlines uterine anatomy and details the genesis and regulation of uterine contractions, emphasizing the electrophysiological role of uterine pacemaker cells, namely interstitial Cajal-like cells. It also provides a thorough overview of current methodologies for assessing uterine contractility, focusing on non-invasive ultrasound-based approaches, and discussing both innovative applications of established techniques and entirely novel diagnostic methods. The review then evaluates the various physiological uterine contractility patterns observed across the menstrual cycle, and finally presents evidence supporting potential causal links between impaired uterine contractility and fertility-threatening uterine pathologies. Since the directionality of this association remains uncertain, longitudinal studies are needed to determine whether alterations in uterine contractility precede or are a consequence of uterine disease. This is a distinction with critical implications for both treatment and prevention strategies in reproductive medicine.

Never a lost cause: can artificial intelligence help embryologists when only poor-quality embryos are available?

Gidel-Dissler N, Canat G, Boyer P … +2 more , Nogueira D, Boussommier-Calleja A

Reprod Biomed Online · 2026 Mar · PMID 41678857 · Publisher ↗

RESEARCH QUESTION: Can EMBRYOLY, an objectively trained artificial intelligence (AI) system, assist embryologists in embryo assessment when only poor-quality embryos are available for transfer? DESIGN: Data from 15,767 e... RESEARCH QUESTION: Can EMBRYOLY, an objectively trained artificial intelligence (AI) system, assist embryologists in embryo assessment when only poor-quality embryos are available for transfer? DESIGN: Data from 15,767 embryos were collected via EMBRYOLY from 3214 egg retrievals (2019-2024) across 15 clinics (four countries) using three time-lapse systems, including data from seven independent clinics (not used in the original training of the algorithm). EMBRYOLY was used to automatically detect poor-quality embryos. Subsequently, EMBRYOLY's transformer-based model was applied on poor-quality embryos to evaluate agreement with embryologists, ranking performances against clinical pregnancy and live birth outcomes, effect on time to pregnancy and first cycle pregnancy rate. Finally, clinical pregnancy rate was compared between poor versus non-poor embryos recommended for transfer by EMBRYOLY's hybrid model. RESULTS: For 29% of embryo cohorts, embryologists were faced with only poor-quality embryos available for transfer. EMBRYOLY's first choice of poor-quality embryo was concordant with the embryologists' first choice in 66% of embryo cohorts. EMBRYOLY's score was significantly associated (P < 0.001) with clinical pregnancies and live births on poor-quality embryos. For multiple transfers of poor-quality embryos, the adjunct use of EMBRYOLY could have reduced cycles to pregnancy by 19% and increased first cycle pregnancy rate by 65%. When EMBRYOLY recommended a poor-quality embryo for transfer, it had comparable chances of leading to a clinical pregnancy compared with higher quality embryos. CONCLUSIONS: Objectively trained AI can help embryologists to select poor-quality embryos that can lead to pregnancy, which is crucial when good or fair embryos are unavailable.

Digital twins in fertility, assisted reproductive technology and pregnancy: a systematic review.

Vallée A, Moawad G, Feki A … +1 more , Ayoubi JM

Reprod Biomed Online · 2026 Mar · PMID 41678856 · Publisher ↗

Digital twins - the term for virtual representations of biological systems - are emerging as promising tools in reproductive medicine. They offer personalized simulations for optimizing fertility, assisted reproductive t... Digital twins - the term for virtual representations of biological systems - are emerging as promising tools in reproductive medicine. They offer personalized simulations for optimizing fertility, assisted reproductive technology (ART) and pregnancy outcomes. However, their use remains limited and fragmented across diverse applications. A systematic search was conducted in PubMed, EMBASE, Scopus and IEEE Xplore up to July 2025 for this review of the current evidence on digital twins in fertility, ART and pregnancy, identifying applications, outcomes, challenges and future prospects. Original studies that applied digital twins to fertility, ART or pregnancy in human or in-silico models were included in this review. Eight original studies were included, complemented by nine mechanistic or conceptual works. Applications encompassed embryo selection, IVF procedure modelling, placental physiology, pregnancy pharmacokinetics, and intrapartum monitoring. Most studies were predictive or descriptive in nature, static or batch-coupled, and at early stages of validation. Risk of bias ranged from moderate to high due to study design and external validity concerns. Only two studies fulfilled strict digital twin criteria, and the exclusion of borderline studies did not change the overall conclusions. Digital twins hold substantial promise for personalized reproductive care. However, their clinical utility remains largely theoretical. Future work must improve modelling accuracy, data integration and ethical implementation to unlock their full potential.

Fertility preservation and family-building in transgender and non-binary patients: 14 years at a UK centre.

Davenport-Pleasance E, Arian-Schad M, Bhattacharya R … +6 more , Rahmati M, Linara-Demakakou E, Macklon N, Rydman K, Garratt J, Ahuja KK

Reprod Biomed Online · 2026 Mar · PMID 41671849 · Publisher ↗

RESEARCH QUESTION: How is assisted reproductive technology used by trans and/or non-binary (TNB) individuals and their partners at London Women's Clinic? DESIGN: This retrospective observational study examined treatments... RESEARCH QUESTION: How is assisted reproductive technology used by trans and/or non-binary (TNB) individuals and their partners at London Women's Clinic? DESIGN: This retrospective observational study examined treatments undertaken by TNB people at London Women's Clinic between 2011 and 2025. Demographic information on patients' age, body mass index, anti-Mullerian hormone, antral follicle count and history of gender-affirming hormone therapy/surgery was analysed. Outcomes included the types of treatment pursued, ongoing pregnancies, and live births. RESULTS: Sixty-four individuals who identified as TNB (n = 42) or had a TNB partner (n = 22) attended the clinic. Treatments included egg freezing (22 cycles), intrauterine insemination (IUI; 17 cycles) and IVF (25 cycles). A minority of IVF cycles involved intra-partner donation (reciprocal IVF; 2/25) or donor eggs (2/25). Three couples' journeys involved surrogacy arrangements. Most TNB individuals attended the clinic with a partner (n = 30), with the exception of those undertaking egg freezing. Of the individuals/couples attempting pregnancy (n =24), most (n =20) were using donor spermatozoa, with the exception of four couples (two involving transgender women who had frozen spermatozoa, and two involving cisgender men). Thirteen live births were achieved and four individuals were discharged from the clinic with ongoing pregnancies. CONCLUSIONS: TNB individuals in the UK are successfully using the spectrum of assisted reproduction options, often with donor gametes and occasionally surrogacy, to build families. In this study, IVF out-performed IUI, underscoring that with inclusive, legally informed care pathways, family formation for TNB patients is both feasible and effective.

Single motherhood by choice in Sweden: survey of unanticipated support needs and financial challenges.

Af Sandeberg Y, Lampic C, Skoog Svanberg A … +4 more , Stenfelt C, Lind AK, Sydsjö G, Elenis E

Reprod Biomed Online · 2026 Mar · PMID 41666667 · Publisher ↗

RESEARCH QUESTION: What are the backgrounds, treatment motives, experiences of mandatory psychosocial evaluation, support needs, post-birth financial circumstances, and reflections on motherhood among single mothers by c... RESEARCH QUESTION: What are the backgrounds, treatment motives, experiences of mandatory psychosocial evaluation, support needs, post-birth financial circumstances, and reflections on motherhood among single mothers by choice who received publicly or privately funded treatment in Sweden? DESIGN: A cross-sectional, anonymous, web-based survey was conducted in 2022 and completed by 256 single mothers by choice with children under five years conceived through assisted reproduction with donated gametes. Outcomes were analyzed by funding source. RESULTS: Participants were aged 28-48 years; 53.9% had received publicly funded treatment. Most (87.1%) held a university, master's, or PhD degree, with a median salary of €3,600. At treatment, 47.7% had been single for more than four years, and 25.4% chose single motherhood for reasons beyond partner absence, such as a desire for sole custody. Obstetric complications were reported by 48.8%. Substantial proportions were dissatisfied with practical support from family or friends (23% and 42%, respectively). After childbirth, 35.5% reduced employment, and 22.7% reported worse-than-expected finances due to unforeseen expenses or instability. Despite these challenges, 98.8% expressed no regret, and 45.3% planned additional children. Findings were largely similar across funding groups. Exceptions included privately funded women, who were older and more likely to report plans to remain voluntarily single, express dissatisfaction with workplace and healthcare support and question the psychosocial evaluation. CONCLUSIONS: Single mothers by choice in Sweden are generally well educated and financially stable at treatment initiation but often face greater-than-expected challenges after childbirth, including medical complications, reduced income, and limited support. Nevertheless, most remain confident in their decision, reflecting long-term planning and strong reproductive agency. Funding source had minimal impact on post-birth financial hardship.

Exposure to endocrine-disrupting chemicals in follicular fluid: implications for assisted reproductive technology outcomes.

Jiang Y, Long X, Hao Y … +3 more , Chen L, Tian T, Zhao Y

Reprod Biomed Online · 2026 Mar · PMID 41662781 · Publisher ↗

RESEARCH QUESTION: Are endocrine-disrupting chemicals (EDC) in follicular fluid associated with assisted reproductive technology (ART) outcomes among women undergoing ART treatment? DESIGN: This prospective cohort study... RESEARCH QUESTION: Are endocrine-disrupting chemicals (EDC) in follicular fluid associated with assisted reproductive technology (ART) outcomes among women undergoing ART treatment? DESIGN: This prospective cohort study involved 176 women who underwent ART treatment in China. The concentrations of 76 EDC, across five categories, in follicular fluid were quantified. Generalized linear models (with and without restricted cubic splines to account for non-linear relationships) and Bayesian kernel machine regression (BKMR) models were utilized. RESULTS: Fifteen EDC exhibited significant negative associations with at least one conventional IVF/intracytoplasmic sperm injection (ICSI) outcome. Notably, mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) was consistently associated with reductions in all conventional IVF/ICSI outcomes, including the numbers of retrieved oocytes, mature oocytes, two pronuclear zygotes, blastocysts and high-quality embryos. Similarly, 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-COOH) was negatively associated with all conventional IVF/ICSI outcomes except the number of blastocysts. No significant negative associations were observed between individual EDC and pregnancy outcomes, including the live birth rate. BKMR model analyses revealed that combinations of EDC were significantly associated with reductions in the numbers of retrieved oocytes and mature oocytes, and the probability of biochemical pregnancy. Among EDC combinations, phthalates (PAE) and bisphenol S (BPS) were identified as dominant contributors to adverse conventional IVF/ICSI outcomes and the biochemical pregnancy rate, respectively. Stratified and interaction analyses further indicated that stronger associations with conventional IVF/ICSI outcomes were observed among women aged ≤33 years. CONCLUSIONS: Elevated concentrations of EDC in follicular fluid were associated with adverse ART outcomes, both as individual compounds and in combination. MECPP, BHT-COOH, PAE and BPS were identified as key EDC. Moreover, the associations were modified by age, with stronger adverse effects observed in younger women.

Synergistic effect of transfer of blastocyst and embryo vitrification on birth weight: a retrospective cohort study.

Li M, Tao Q, Zhao Z … +6 more , Huang J, Lian Y, Liu P, Li Q, Li R, Qiao J

Reprod Biomed Online · 2026 Mar · PMID 41655327 · Publisher ↗

RESEARCH QUESTION: Does the synergistic interaction between blastocyst-stage embryo transfer and vitrification in assisted reproductive technology increase the risk of adverse neonatal outcomes, specifically elevated bir... RESEARCH QUESTION: Does the synergistic interaction between blastocyst-stage embryo transfer and vitrification in assisted reproductive technology increase the risk of adverse neonatal outcomes, specifically elevated birth weight z-scores and a higher incidence of clinically concerning large for gestational age (LGA) or macrosomia in offspring? DESIGN: In this cohort study, multivariable regression analyses were conducted to examine the association between embryo transfer strategies (fresh versus frozen; cleavage versus blastocyst stage) and the birth weight z-score of singletons, as well as the incidence of LGA and macrosomia among 42,190 singleton live births from the Center for Reproductive Medicine at Peking University Third Hospital between 2012 and 2022. RESULTS: Compared with cleavage-stage embryo transfer, newborns resulting from blastocyst-stage transfers had significantly higher birth weight z-scores (P < 0.001), LGA (P < 0.001) and macrosomia (P = 0.013). Frozen embryo transfer (only vitrified-warmed) was associated with increased birth weight z-scores (P = 0.001), LGA (P = 0.004) and macrosomia (P = 0.007), compared with fresh embryo transfers. A significant synergetic effect of blastocyst transfer and vitrified-warmed transfer concerning the LGA was found (relative excess risks due to interaction = 0.24; 95% CI 0.06 to 0.42; P = 0.022 for multiplicative interaction term) on the additive and multiplicative scales. CONCLUSIONS: Blastocyst stage and embryo vitrification were associated with elevated birth weight z-scores and an increased likelihood of LGA, with evidence of a synergistic effect. These findings support the importance of personalized clinical decision-making in the use of vitrified-warmed cleavage-stage transfer, particularly in the absence of clear medical indications.
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