Reproductive Biomedicine Online[JOURNAL]
Sun
200 papers
Corpus luteum formation in frozen embryo transfer and offspring growth trajectories: a prospective cohort study.
Xia X, Ge J, Dou Y … +11 more , Chang J, Jiang Y, Lv H, Du J, Jiang T, Xu X, Chen Y, Yu C, Lu R, Hu L, Lin Y
Reprod Biomed Online · 2026 Feb · PMID 42202668 · Publisher ↗
RESEARCH QUESTION: What are the effects of different endometrial preparation protocols in frozen embryo transfer (FET) cycles on offspring growth, and does the presence or absence of corpus luteum formation influence gro...
RESEARCH QUESTION: What are the effects of different endometrial preparation protocols in frozen embryo transfer (FET) cycles on offspring growth, and does the presence or absence of corpus luteum formation influence growth trajectories of children from birth to 3 years? DESIGN: Prospective cohort study based on the Jiangsu Birth Cohort (n = 1956 singleton live births after FET between November 2017 and October 2022). Participants were categorized into the 'corpus luteum forming' (CLF), including true natural, modified natural and ovulation induction cycles, and 'non-corpus luteum forming' (NCLF), including artificial and GnRHa downregulated artificial cycles groups. Offspring anthropometric measures were collected at nine time points to 3 years. Z-scores were calculated using WHO 2006 standards. Linear mixed models (LMM) and group-based trajectory modelling (GBTM) assessed group differences in growth, adjusting for socioeconomic, maternal and child factors. RESULTS: Among 1956 families (NCLF: n = 1408; CLF: n = 548), birth measures were comparable. The NCLF group showed lower weight, BMI and related z-scores at 18 months, and lower head circumference z-scores at 24 months, with these differences resolving by 3 years; LMM revealed significantly lower weight-for-age z-scores between 8 and 30 months and lower length-for-age z-scores at 30 months in the NCLF group; and GBTM identified three distinct patterns for both indicators, with no significant differences in trajectory group distribution between groups. CONCLUSIONS: Corpus luteum formation affects early weight and length growth trajectories but has no lasting effect by age 3 years. The developmental safety of different endometrial preparation protocols in children conceived through assisted reproduction is supported.
Free pelvic fluid detection and quantification using transvaginal ultrasound: a surrogate marker for retrograde menstruation.
Salmeri N, Viganò P, Reschini M … +5 more , Schironi E, Tuccitto M, Filippi F, Vercellini P, Somigliana E
Reprod Biomed Online · 2026 Mar · PMID 42202667 · Publisher ↗
RESEARCH QUESTION: Can transvaginal ultrasonography (TVUS) reliably detect and quantify free pelvic fluid (FPF) as a surrogate marker of retrograde menstruation, and how do its volume and characteristics vary across mens...
RESEARCH QUESTION: Can transvaginal ultrasonography (TVUS) reliably detect and quantify free pelvic fluid (FPF) as a surrogate marker of retrograde menstruation, and how do its volume and characteristics vary across menstrual phases, characteristics and gynaecological conditions? DESIGN: Prospective, observational, single-centre cohort study at a tertiary infertility centre. Women underwent two standardized TVUS examinations within the same natural menstrual cycle: on day 2-3 (menstrual phase) and day 7-10 (medium-late proliferative phase). FPF volume was measured using the ellipsoid formula, and within-cycle changes (ΔVRM) were calculated. The primary outcome was the presence and extent of FPF and within-cycle FPF changes, and the secondary outcome was menstrual-phase FPF changes across menstrual blood loss (MBL) categories. RESULTS: In total, 102 women were included in this study. FPF was detected in 71.6% (95% CI 61.8-80.1%) on day 2-3 and in 44.1% (95% CI 34.3-54.3%) on day 7-10 (P < 0.001). Among women with measurable FPF (n = 73), ΔVRM was positive in 73% (95% CI 61.4-82.7%; P < 0.001), significantly different from the 50% expected under no within-cycle difference. Median FPF volume declined from 1.0 ml (IQR 0.3-3.2) ml in the menstrual phase to 0 ml (IQR 0-0.6 ml) in the proliferative phase (P < 0.001). Menstrual FPF >1 ml was observed in 0% (0/4), 43.9% (18/41) and 60.7% (17/28) of women with scanty, normal and heavy MBL, respectively (P = 0.03). CONCLUSION: Menstrual FPF was detected in over two-thirds of women, with within-cycle volumetric changes, wide variability between women, and increasing magnitude with heavier MBL. These findings suggest that, using FPF as a surrogate marker, retrograde menstruation may be identified and quantified using a simple non-invasive TVUS-based method. This work offers a potential methodological framework for studying menstrual physiology.
Improved clinical outcomes with one-step warming of vitrified blastocysts: a retrospective analysis of 3167 transfers.
Yelke HK, Çetinkaya CP, Aygün TM … +4 more , Selimoğlu S, Yıldız S, Çolakoğlu YK, Kahraman S
Reprod Biomed Online · 2026 Feb · PMID 42184780 · Publisher ↗
RESEARCH QUESTION: Does a one-step warming protocol for vitrified blastocysts improve post-warming recovery, clinical outcomes and neonatal safety compared with a conventional multi-step warming method? DESIGN: A retrosp...
RESEARCH QUESTION: Does a one-step warming protocol for vitrified blastocysts improve post-warming recovery, clinical outcomes and neonatal safety compared with a conventional multi-step warming method? DESIGN: A retrospective analysis of 3167 vitrified blastocyst warming cycles compared outcomes between a one-step protocol (n = 1750) and a conventional multi-step protocol (n = 1417). Key outcomes included post-warming survival and re-expansion, biochemical and clinical pregnancy rates, ongoing pregnancy rate, live birth rate, neonatal parameters (gestational age, birth weight) and miscarriage rate. Subgroup analyses were performed in Society for Assisted Reproductive Technology age groups and preimplantation genetic testing for aneuploidy (PGT-A) cycles. RESULTS: Post-warming survival exceeded 99% in both groups. Early re-expansion (0-2 h) was higher for the multi-step warming protocol, but by 4 h, the one-step warming protocol showed better expansion in the total cohort. The one-step warming protocol achieved significantly higher rates of β-human chorionic gonadotrophin positivity (77.7% versus 73.5%), clinical pregnancy (72.1% versus 67.2%), ongoing pregnancy (66.5% versus 61.2%) and live birth (63.7% versus 57.0%; all P < 0.001) in the total cohort. In patients aged <35 years, ongoing pregnancy and live birth rates were significantly higher with the one-step warming protocol (68.9% versus 64.0%, P = 0.04; 66.8% versus 59.6%, P = 0.003). In the same age group with PGT-A, clinical pregnancy improved significantly (78.8% versus 71.9%; P = 0.019). Live births across age groups were numerically higher with the one-step warming protocol, although the differences did not achieve significance, and neonatal outcomes were comparable between protocols. CONCLUSIONS: One-step warming is a safe and effective alternative to conventional multi-step warming. It improves clinical outcomes, particularly in younger patients and euploid embryo transfers, while maintaining neonatal safety and streamlining laboratory workflows.
Increased risk of thromboembolism in adenomyosis: a case-control study.
Hiratsuka D, Matsuo M, Ishizawa C … +7 more , Fukui Y, Aikawa S, Hiraoka T, Makabe T, Izumi G, Harada M, Hirota Y
Reprod Biomed Online · 2026 Apr · PMID 42184779 · Publisher ↗
RESEARCH QUESTION: Does adenomyosis increase the risk of thromboembolic events, including both arterial and venous thromboembolism, compared with endometriosis, and what clinical factors may contribute to this associatio...
RESEARCH QUESTION: Does adenomyosis increase the risk of thromboembolic events, including both arterial and venous thromboembolism, compared with endometriosis, and what clinical factors may contribute to this association? DESIGN: This retrospective case-control study was conducted at the University of Tokyo Hospital. In total, 1826 symptomatic women were included, comprising 745 women diagnosed with adenomyosis and 1081 women with endometriosis without adenomyosis. To minimize confounding by age, an established risk factor for thromboembolism, 712 age-matched pairs were analysed. The prevalence and types of thromboembolic events were compared between groups, and clinical characteristics such as anaemia and oestrogen exposure were evaluated. RESULTS: A history of thromboembolism was identified in 2.7% (20/745) of patients with adenomyosis and 0.5% (5/1081) of patients with endometriosis (P < 0.001). After age adjustment, the difference remained significant (2.8% versus 0.7%; P = 0.005). Venous thromboembolism was more common in patients with adenomyosis than in patients with endometriosis (2.4% versus 0.7%; P = 0.019). Arterial thromboembolism occurred in the adenomyosis group alone (0.4%). Among patients with adenomyosis with a history of thromboembolism, 75% had anaemia (haemoglobin < 10 g/dl) and 75% had a history of high oestrogen exposure (use of oestrogen-containing medications or pregnancy). In multivariable logistic regression analysis, anaemia remained significantly associated with thromboembolism (OR 5.60, 95% CI 1.55-24.30). CONCLUSIONS: Adenomyosis is associated with significantly higher prevalence of thromboembolism compared with endometriosis. Anaemia may further increase susceptibility, underscoring the importance of assessment of the risk of thromboembolism in women with adenomyosis.
Rethinking the route of oocyte retrieval: when one procedure does not fit all.
Melado L, Lawrenz B, Fatemi H
Reprod Biomed Online · 2026 Apr · PMID 42176530 · Publisher ↗
Transvaginal ultrasound-guided oocyte retrieval is widely regarded as the gold standard in assisted reproduction and fertility preservation. For most women, this approach is safe, efficient and effective. However, anatom...
Transvaginal ultrasound-guided oocyte retrieval is widely regarded as the gold standard in assisted reproduction and fertility preservation. For most women, this approach is safe, efficient and effective. However, anatomical variations, previous pelvic surgery and cultural considerations may render transvaginal access difficult or unacceptable. Alternative routes (transabdominal, transrectal and laparoscopic) are established, evidence-based techniques that can be considered when transvaginal oocyte retrieval is not feasible. This Countercurrent does not examine the superiority of any access route for oocyte retrieval but rather advocates for reproductive medicine to broaden its procedural repertoire to offer truly customized treatment for a diverse global patient demographic.
Artificial intelligence-driven oocyte scores are associated with early morphokinetics and embryo outcomes after intracytoplasmic sperm injection.
Fujiwara N, Ezoe K, Miki T … +8 more , Takahashi T, Vanzella L, Mercuri N, Fjeldstad J, Mojiri P, Nayot D, Kuroda T, Kato K
Reprod Biomed Online · 2025 Oct · PMID 42176529 · Publisher ↗
RESEARCH QUESTION: How are the scores obtained using the deep learning-based oocyte assessment system, MAGENTA, associated with outcomes of intracytoplasmic sperm injection (ICSI) and biological events during the preimpl...
RESEARCH QUESTION: How are the scores obtained using the deep learning-based oocyte assessment system, MAGENTA, associated with outcomes of intracytoplasmic sperm injection (ICSI) and biological events during the preimplantation period? DESIGN: Retrospective study of 2785 images of mature oocytes from 1340 retrieval cycles. Images were obtained immediately after ICSI from time-lapse systems and scored by MAGENTA. Key phenomena, including pronuclear and cytoplasmic dynamics, cleavage patterns, blastomere compaction and embryo quality were manually annotated. The relationships between the MAGENTA score and embryonic and pregnancy outcomes, and morphokinetics were analysed using generalized linear models with generalized estimating equations to account for clustering. RESULTS: Oocytes in the lower MAGENTA scores showed higher degeneration rates (P < 0.001) and lower normal fertilization rates (P < 0.001) per ICSI. Higher MAGENTA scores were associated with increased likelihood of development to the two- and eight-cell stages, compaction, blastulation and blastocyst expansion (all P < 0.001). Lower MAGENTA scores were associated with the following: delayed fertilization events, including second polar body extrusion, cytoplasmic wave initiation, halo redistribution and disappearance, and pronuclear appearance and breakdown (all P < 0.001); delayed first cleavage and higher incidences of abnormal cleavage, aberrant blastomere movement, and multinucleation (all P ≤ 0.001); and early compaction (P = 0.040), blastomere exclusion (P < 0.001) and poor inner cell mass and trophectoderm morphology (all P < 0.001). The sum of MAGENTA scores for all oocytes per retrieval cycle was positively associated with the cumulative live birth rate (P < 0.001). CONCLUSIONS: The MAGENTA score is associated with key fertilization dynamics, cleavage abnormalities, compaction behaviour and blastocyst development, providing a quantitative indicator of oocyte developmental competence.
Informed opinion: the mating gap.
Inhorn MC
Reprod Biomed Online · 2026 Apr · PMID 42167088 · Publisher ↗
An anthropological study of 150 American women who froze their eggs has revealed a 'mating gap'. Namely, highly educated, heterosexual, professional women want the three P's of partnership, pregnancy and parenthood, but...
An anthropological study of 150 American women who froze their eggs has revealed a 'mating gap'. Namely, highly educated, heterosexual, professional women want the three P's of partnership, pregnancy and parenthood, but are missing the three E's of eligible, educated and equal male partners. Thus, they turn to egg freezing to preserve and extend their fertility while waiting for a mate who may or may not materialize. Gender-based educational disparities underlie this mating gap. Women around the world are significantly outperforming men in higher education, leaving a massive undersupply of educated male partners for women in their prime reproductive years. Furthermore, men's lower commitments to partnership and family building are lamented by women, who face difficult choices regarding their reproductive futures. Women's three family-building options are: (i) egg freezing to preserve and extend fertility while waiting for an equal partner; (ii) pursuing single motherhood by choice through sperm donation; or (iii) testing 'mixed-collar mating' (hypogamy) with a less-educated man. Given the growing mating gap in many countries, hypogamy may become increasingly necessary - and a potentially successful strategy - for women who hope to find a loving mate and devoted father for their children.
Investigating DNA contamination affecting embryo biopsy specimens taken for PGT-A: Incidence and impact on the accuracy of chromosomal analysis.
Clark G, Babariya D, Kilbee M … +5 more , Fernández Marcos E, Haj Ali A, Ceban V, Capalbo A, Wells D
Reprod Biomed Online · 2026 Feb · PMID 42167074 · Publisher ↗
RESEARCH QUESTION: What is the prevalence of DNA contamination in embryo biopsy samples taken for preimplantation genetic testing for aneuploidy (PGT-A), and how often might contamination lead to incorrect interpretation...
RESEARCH QUESTION: What is the prevalence of DNA contamination in embryo biopsy samples taken for preimplantation genetic testing for aneuploidy (PGT-A), and how often might contamination lead to incorrect interpretation of results? DESIGN: A retrospective study of 57,292 clinical PGT-A samples from 32 IVF clinics was carried out to determine the frequency of DNA contamination affecting trophectoderm biopsy specimens. Testing employed a highly validated and widely used PGT-A method, which includes genotyping of >4000 single-nucleotide polymorphisms. RESULTS: Validation experiments confirmed the ability of the method to detect DNA contamination reliably. Overall, contamination was detected in 0.45% (256/57,292) of trophectoderm biopsy specimens, but rates at individual clinics varied significantly (P < 0.0001, chi-squared test). In total, 155 embryos with a contaminated biopsy specimen had a result from a second (uncontaminated) sample. Comparison of the two biopsies revealed that errors in classification of chromosomal status could have occurred in 44.5% (69/155) of these embryos if contamination had not been detected. CONCLUSIONS: DNA contamination affected one in 222 samples. However, frequencies below one in 1000 were achieved in some clinics, while the incidence of contamination was more than 10 times higher at other clinics. Contamination was associated with a substantial risk of diagnostic error, potentially leading to the discard of viable embryos or the transfer of aneuploid embryos. Validated PGT-A methods, capable of detecting DNA contamination, should be used, and the incidence of contamination should be considered a key performance indicator for clinics offering PGT-A.
Luteal phase progesterone support in modified natural cycle frozen embryo transfer: a systematic review and meta-analysis.
Engesgaard FM, Johansen AS, Saupstad M … +3 more , Wang NF, Pinborg A, Løssl K
Reprod Biomed Online · 2026 Apr · PMID 42160980 · Publisher ↗
Modified natural cycle frozen embryo transfer (mNC-FET) using an exogenous human chorionic gonadotrophin (HCG) trigger is a widely used endometrial preparation protocol. The need for luteal phase support (LPS) in mNC-FET...
Modified natural cycle frozen embryo transfer (mNC-FET) using an exogenous human chorionic gonadotrophin (HCG) trigger is a widely used endometrial preparation protocol. The need for luteal phase support (LPS) in mNC-FET remains uncertain. The primary outcome of this systematic review and meta-analysis was the impact of progesterone LPS on the live birth rate (LBR). Secondary outcomes included clinical pregnancy rate (CPR) and pregnancy loss rate (PLR). A systematic literature search identified eight eligible studies, of which seven [three randomized controlled trials (RCT) and four retrospective cohort studies] were included in the meta-analysis, comprising 3896 cycles. Five studies, including the three RCT, found no benefit of progesterone LPS in mNC-FET. Using study-reported OR and adjusted OR (aOR), the meta-analysis showed no difference in LBR between progesterone LPS and no LPS (OR 1.15, 95% CI 0.98-1.36; aOR 1.07, 95% CI 0.64-1.79). CPR increased with LPS in the crude analysis (OR 1.21, 95% CI 1.04-1.40), but not in the adjusted analysis (aOR 1.15, 95% CI 0.87-1.51). PLR was similar between LPS and no LPS (OR 0.98, 95% CI 0.70-1.38). These results do not support a general benefit of progesterone LPS in mNC-FET. It remains to be determined whether certain subgroups require an individualized approach.
Effectiveness of fertility health awareness strategies on fertility knowledge and childbearing: a randomized controlled trial.
Chan SL, Thumboo J, Boivin J … +7 more , Zhan SJ, Saffari SE, Yeo SR, Chan JKY, Ku CW, Chua KH, Yu SL
Reprod Biomed Online · 2026 Feb · PMID 42160979 · Publisher ↗
RESEARCH QUESTION: What is the effect of fertility health screening (FHS) and fertility awareness tools (FAT) on parenthood intentions, as measured by the wife's intended age at first birth, compared with no intervention...
RESEARCH QUESTION: What is the effect of fertility health screening (FHS) and fertility awareness tools (FAT) on parenthood intentions, as measured by the wife's intended age at first birth, compared with no intervention, 6 months after randomization? DESIGN: An effectiveness-implementation hybrid type I trial with a multicentre three-arm parallel group open-label randomized controlled trial. Married Singaporean couples with wives aged between 25 and 34 years were randomized to FHS, FAT or no intervention. The primary outcome was the wife's intended age at first birth. Secondary outcomes included fertility knowledge, attempts to conceive, pregnancy and pursuing further fertility screening, treatment, or both, 6 months after randomization. RESULTS: A total of 778 couples were randomized to the FHS (n = 226), FAT (n = 238) and control (n = 314) groups, respectively. Compared with the control group, no significant difference for either FHS or FAT was seen regarding the change in the wife's intended age at first birth at follow-up (0.07, 95% CI ‒0.17 to 0.32 and ‒0.01, 95% CI ‒0.25 to 0.23 years, respectively). Both interventions significantly increased fertility awareness, as measured by the mean increase in Cardiff Fertility Knowledge Score in wives (FHS, 0.38, 95% CI 0.03 to 0.73; FAT, 0.44, 95% CI 0.10 to 0.79 and husbands (FHS, 0.41, 95% CI 0.04 to 0.78; FAT 0.71, 95% CI 0.35 to 1.10). No significant differences were observed in all other secondary outcomes. CONCLUSION: Neither FHS nor FAT significantly modified parenthood intentions 6 months after randomization.
Electroacupuncture alleviates endometriosis by suppressing ferroptosis in murine ectopic and eutopic endometria via the Nrf2 pathway.
Zan Y, Zhuang Y, Zhu Q … +4 more , Huang X, Li J, Xia L, Xia Y
Reprod Biomed Online · 2026 Feb · PMID 42155249 · Publisher ↗
RESEARCH QUESTION: Does peritoneal iron overload drive fibrosis in endometriosis through Nrf2 pathway dysfunction and the resulting ferroptosis, and can electroacupuncture intervene in this process? DESIGN: An endometrio...
RESEARCH QUESTION: Does peritoneal iron overload drive fibrosis in endometriosis through Nrf2 pathway dysfunction and the resulting ferroptosis, and can electroacupuncture intervene in this process? DESIGN: An endometriosis mouse model was established by intraperitoneal injection of syngeneic uterine fragments combined with periodic injection of whole blood, and subjected to electroacupuncture intervention. Fibrosis, ferroptosis-related markers, Nrf2/Keap1 pathway activity, the peritoneal microenvironment and systemic pathological indicators were systematically assessed using histological staining, molecular biology techniques and biochemical analyses. RESULTS: Eutopic uterus and ectopic lesions in mice with endometriosis had significant fibrosis (P < 0.01) accompanied by pronounced ferroptosis (P < 0.01). Mechanistically, the Nrf2 pathway was functionally inactivated in these tissues, with impaired nuclear translocation (P < 0.01). Notably, in the eutopic uterus, this inhibition occurred independently of its classical regulatory protein Keap1, suggesting alternative regulatory mechanisms for Nrf2. Electroacupuncture treatment effectively suppressed lesion growth (P < 0.05) alleviated fibrosis (P < 0.01) and ferroptosis (P < 0.01), and also specifically reversed the impairment of Nrf2 nuclear translocation (P < 0.01) and improved systemic inflammation and endocrine disturbances. CONCLUSIONS: To our knowledge, this study is the first to systematically demonstrate the pivotal role of the 'Nrf2 pathway inactivation‒ferroptosis‒fibrosis' axis in endometriosis, particularly in the eutopic uterus. Our findings provide a novel paradigm for understanding the pathological mechanisms of endometriosis and confirms that electroacupuncture exerts therapeutic effects by targeting this pathway, offering a solid experimental foundation for its clinical application.
Polarized light microscopy reveals distinct spindle phenotypes and outcomes in non-pronuclear zygotes.
Ma M, Liao X, Chen C … +7 more , Yu L, Yang J, Li M, Zhao X, Zhao L, Jin W, Lyu Q
Reprod Biomed Online · 2025 Nov · PMID 42150319 · Publisher ↗
RESEARCH QUESTION: Can polarized light microscopy (PLM) spindle phenotypes predict the developmental potential of non-pronuclear (0PN) zygotes? DESIGN: Retrospective observational study including 1266 0PN zygotes and 69,...
RESEARCH QUESTION: Can polarized light microscopy (PLM) spindle phenotypes predict the developmental potential of non-pronuclear (0PN) zygotes? DESIGN: Retrospective observational study including 1266 0PN zygotes and 69,383 two-pronuclei (2PN) zygotes from patients undergoing IVF and embryo transfer treatments in a reproductive centre affiliated to a university hospital from June 2021 to November 2024. Phenotypic observations were obtained through PLM; all 0PN zygotes were categorized into four distinct groups: adjacent dual spindles (AD-SP); separate dual spindles (SD-SP); mono-spindle (M-SP) and no spindle (N-SP). Logistic regression assessed the effect of these PLM phenotypes on embryological outcomes, considering parental and treatment factors, and evaluated the effects of rescue artificial oocyte activation or rescue ICSI on these outcomes. RESULTS: Cleavage rates were significantly lower in AD-SP (adjusted odds ratio [aOR] 0.22; P < 0.001), SD-SP (aOR 0.03; P < 0.001), M-SP (aOR 0.02; P < 0.001), and N-SP (aOR 0.02; P < 0.001) categories compared with 2PN zygotes. The rates of four or more cells at day 3 (aOR 1.97; P = 0.041), six or more cells on day 3 (aOR 1.60; P = 0.012) and good-quality embryos at day 3 (aOR 1.58; P = 0.008) were significantly higher in AD-SP categories compared with 2PN zygotes. Blastocyst formation rates of day-3 poor-quality embryos (aOR 1.31; P = 0.351) was comparable between 2PN zygotes and 0PN zygotes with AD-SP. CONCLUSIONS: Four prominent phenotypes of 0PN zygotes were identified based on PLM, along with their corresponding embryonic outcomes. Notably, 0PN zygotes with AD-SP had embryonic outcomes similar to those of 2PN zygotes, except for cleavage rate, and demonstrated superior developmental potential compared with other phenotypes.
Association between blastocyst morphometrics and live birth, obstetric complications and perinatal outcomes.
Utsuno H, Ishimaru T, Matsumoto M … +4 more , Takahashi H, Kamijo S, Yamada M, Tanaka M
Reprod Biomed Online · 2026 Feb · PMID 42150318 · Publisher ↗
RESEARCH QUESTION: Are blastocyst morphometrics, specifically diameter, inner cell mass (ICM) area and trophectoderm (TE) cell count, associated with live birth, obstetric complications and perinatal outcomes? DESIGN: Th...
RESEARCH QUESTION: Are blastocyst morphometrics, specifically diameter, inner cell mass (ICM) area and trophectoderm (TE) cell count, associated with live birth, obstetric complications and perinatal outcomes? DESIGN: This retrospective single-centre cohort study involved 1132 vitrified-warmed single-blastocyst transfers performed between May 2018 and July 2024. Blastocyst diameter, ICM area and TE cell count were quantitatively measured before vitrification. The effects of blastocyst morphometric parameters on live birth, obstetric complications and perinatal outcomes were evaluated using statistical models that accounted for potential confounding factors. RESULTS: Each 100 μm increase in ICM area and each 10-cell increase in TE cell count was associated with increased live birth rates (ICM area: marginal odds ratio [mOR] 1.023, 95% CI 1.009-1.037, P = 0.001; TE cell count: mOR 1.101, 95% CI 1.038-1.168, P = 0.001). Each 10-cell increase in TE cell count was significantly associated with increased birthweight (β = 19.47 g, 95% CI 4.91-34.02 g, P = 0.010) and placental weight (β = 8.64 g, 95% CI 3.00-14.27 g, P = 0.003), as well as with a reduced risk of low birthweight (LBW; mOR 0.860, 95% CI 0.743-0.995, P = 0.044), small for gestational age (SGA; mOR 0.693, 95% CI 0.541-0.888, P = 0.004) and hypertensive disorders of pregnancy (HDP; mOR 0.740, 95% CI 0.600-0.912, P = 0.005). CONCLUSIONS: Both ICM area and TE cell count were independently associated with live births following embryo transfer. Once pregnancy is established, TE morphology, specifically TE cell count, further influences birthweight, placental weight and incidence of LBW, SGA and HDP.
Back to the future! Is there still a role for the GnRH agonist protocol in ovarian stimulation?
Kalaitzopoulos DR, Voros C, Blockeel C
Reprod Biomed Online · 2026 Apr · PMID 42143849 · Publisher ↗
For more than two decades, gonadotrophin-releasing hormone (GnRH) agonist protocols were used as the standard stimulation regimen in IVF, due to the effective prevention of premature LH surges and reduced cycle cancellat...
For more than two decades, gonadotrophin-releasing hormone (GnRH) agonist protocols were used as the standard stimulation regimen in IVF, due to the effective prevention of premature LH surges and reduced cycle cancellation rates. Over the past two decades, however, their use has markedly declined with the widespread adoption of GnRH antagonist and progestin-primed ovarian stimulation protocols, which offer shorter treatment durations and greater patient convenience. This article examines the contemporary evidence on GnRH agonist protocols and identifies patient subgroups in whom their use may remain clinically relevant.
L-carnitine ameliorates decidualization in high-fat diet-induced obese rats and human endometrial stromal cells treated with palmitic acid.
Cao H, Qi D, Sun N … +4 more , Sun P, Xue P, Sun P, Ma H
Reprod Biomed Online · 2026 Jan · PMID 42143848 · Publisher ↗
RESEARCH QUESTION: Does L-carnitine ameliorate impairment of endometrial decidualization in high-fat diet-induced obese rats and human endometrial stromal cells (HESC) treated with palmitic acid-treated? DESIGN: Obese fe...
RESEARCH QUESTION: Does L-carnitine ameliorate impairment of endometrial decidualization in high-fat diet-induced obese rats and human endometrial stromal cells (HESC) treated with palmitic acid-treated? DESIGN: Obese female rats (n = 10 per group; 5 weeks old at commencement of dietary intervention) induced by a high-fat diet for 8 weeks were administered L-carnitine at doses of 135, 400 and 1200 mg/kg/day via oral gavage for 5 weeks, with metformin serving as the control. After mating, uterine specimens were collected on gestational day 7 and analysed by various techniques, including haematoxylin and eosin staining, and Western blotting. Additionally, palmitic acid was used to induce lipid accumulation in immortalized HESC, followed by treatment with L-carnitine to investigate its effects on decidualization processes. RESULTS: Compared with metformin, the administration of L-carnitine (400 mg/kg/day) restored the number of embryo implantation sites and decidualization in vivo. L-carnitine was found to increase the expression of sirtuin 1 (SIRT1) and Forkhead box class O 1 (FOXO1), while simultaneously decreasing expression of acetyl-FOXO1. In vitro, L-carnitine reversed the palmitic acid-induced suppression of decidualization markers and restored mitochondrial polarization. Notably, L-carnitine treatment restored SIRT1/FOXO1 signalling pathways and enhanced the expression of the progesterone receptor in vivo and in vitro. CONCLUSIONS: L-carnitine ameliorates impaired endometrial decidualization in rats fed a high-fat diet and HESC treated with palmitic acid via the SIRT1/FOXO1/progesterone receptor pathway.
Decidual senescence in recurrent pregnancy loss: forkhead box M1-targeted progesterone treatment.
Kendirci-Katirci R, Katirci E, Sanhal CY … +3 more , Kirtis E, Sati L, Celik-Ozenci C
Reprod Biomed Online · 2026 Feb · PMID 42143847 · Publisher ↗
RESEARCH QUESTION: What is the role of FOXM1 in the pathogenesis of recurrent pregnancy loss (RPL) characterized by increased decidual senescence, and how do two progesterone analogues (medroxyprogesterone acetate [MPA]...
RESEARCH QUESTION: What is the role of FOXM1 in the pathogenesis of recurrent pregnancy loss (RPL) characterized by increased decidual senescence, and how do two progesterone analogues (medroxyprogesterone acetate [MPA] and dydrogesterone [DYD]) modulate FOXM1 expression and associated senescence markers in an in-vitro decidualization model? DESIGN: Primary decidual cells were isolated from decidual tissue samples collected from women with clinically healthy pregnancies that were terminated voluntarily (control pregnancy group, n = 10) and women with RPL (RPL group, n = 10). Cells were treated with MPA and DYD, and PRL and IGFBP-1 concentrations were analysed by ELISA. FOXO1, FOXM1, phospho-FOXM1 (p-FOXM1), DIO2 and β-GAL expression was examined by immunofluorescence. Co-culture experiments with AC-1M88 trophoblast-like cells assessed spheroid expansion and migration. RESULTS: MPA and DYD treatments significantly ameliorated PRL (P = 0.006 and P = 0.015, respectively) and IGFBP-1 (both P < 0.001) concentrations, and FOXO1, FOXM1 and p-FOXM1 expression (all P < 0.001), in the RPL group. DYD treatment was more effective than MPA treatment in restoring FOXM1 and p-FOXM1 expression (both P < 0.001). MPA and DYD did not affect spheroid expansion in the RPL group but increased cell migration (p=0.009 and p<0.001, respectively); however, neither treatment significantly reduced DIO2 or β-GAL expression. CONCLUSIONS: Decidual cells from women with RPL exhibited reduced FOXM1 expression and increased senescence-associated markers. MPA and DYD restored FOXM1 expression and improved decidual function, but did not reverse senescence marker expression. These findings suggest that combining senomorphic agents with progesterone analogues may represent a promising avenue for future mechanistic and translational research.
Changing the paradigm of endometriosis - from diagnosis to integrated long-term management: a joint society opinion paper.
Chapron C, Parpex G, Van den Bosch T … +7 more , Al-Hendy A, Gargiulo A, Stockwell E, Taylor HS, McCarus S, Petraglia F, Society of Endometriosis and Uterine Disorders (SEUD) and American Institute for Minimally Invasive Surgery (AIMIS)
Reprod Biomed Online · 2026 Feb · PMID 42140173 · Publisher ↗
Endometriosis is a chronic, systemic, oestrogen-dependent disease with major impacts on pain, fertility and quality of life. This Society of Endometriosis and Uterine Disorders and American Institute for Minimally Invasi...
Endometriosis is a chronic, systemic, oestrogen-dependent disease with major impacts on pain, fertility and quality of life. This Society of Endometriosis and Uterine Disorders and American Institute for Minimally Invasive Surgery opinion synthesizes current evidence to redefine diagnostic and therapeutic strategies across the continuum of care. Diagnostic laparoscopy is no longer indicated, as clinical assessment combined with expert transvaginal ultrasonography and magnetic resonance imaging reliably identifies disease phenotypes and guides management. Medical therapy, particularly progestins, remains the foundation of long-term care, with gonadotrophin-releasing hormone analogues and antagonists as second-line options. Surgery is reserved for clearly defined indications - including deep infiltrating disease, infertility with correctable anatomy and organ-threatening involvement - and must be preceded by comprehensive imaging and followed by prolonged hormonal suppression to reduce recurrence. Integrated, individualized care pathways are essential to improve outcomes and support fertility preservation. This framework represents a modern paradigm for comprehensive endometriosis management.
Improving embryo ploidy prediction: a machine learning approach using morphokinetic meta-variables and clinical data.
Güell-Penas E, Ferrer-Buitrago M, Robles EFI … +13 more , Lliso CC, Rugero FM, Olmedo PN, Rodié EVI, Rubira MJL, Arcos IM, Álvarez ES, Soler LM, Riuró EF, Miguel ISÁ, Méndez EP, López AM, Pérez JIM
Reprod Biomed Online · 2025 Nov · PMID 42134027 · Publisher ↗
RESEARCH QUESTION: Can a machine learning model integrating time-lapse morphokinetic meta-variables with clinical data predict embryo aneuploidy accurately for improved non-invasive embryo selection? DESIGN: A retrospect...
RESEARCH QUESTION: Can a machine learning model integrating time-lapse morphokinetic meta-variables with clinical data predict embryo aneuploidy accurately for improved non-invasive embryo selection? DESIGN: A retrospective multicentre cohort study using time-lapse data from 1190 blastocysts from nine Spanish fertility clinics (2017-2024), with 70% (n = 833) and 30% (n = 357) used for model training/testing and external validation, respectively. The primary dataset included well-defined outcomes (live birth or aneuploidy diagnosis via preimplantation genetic testing). The LIFE Predict v1.1 model integrated clinical data and novel morphokinetic meta-variables (range and mean absolute error) representing deviations from expected embryo development. Model performance was assessed using area under the receiver operating characteristic curve (AUC-ROC) and confusion matrix metrics. Logistic regression was used to calculate OR for risk of aneuploidy. Morphological assessments using ASEBIR grading were combined with algorithmic scoring. RESULTS: The final ensemble model achieved an AUC of 0.824 (95% CI 0.796-0.857) in cross-validation and 0.818 (95% CI 0.794-0.851) in external validation. The LIFE Predict v1.1 score showed a significant inverse relationship with risk of aneuploidy, with each one-point decrease increasing the odds of aneuploidy by 76% (OR = 1.76, 95% CI 1.52-2.05). The aneuploidy rate decreased across ascending score quartiles: 76.4% (lowest), 64.0%, 25.8% and 13.3% (highest). Combining morphological grading with the LIFE Predict v1.1 model revealed substantial risk stratification within identical morphological categories, with A-grade (Day 5) embryos showing aneuploidy rates from 11-14% (highest score quartiles) to 60-86% (lowest quartiles). CONCLUSIONS: The LIFE Predict v1.1 model predicts embryo outcomes accurately using morphokinetic meta-variables and clinical data, providing actionable risk stratification that complements conventional morphological assessment for enhanced non-invasive embryo selection. Prospective clinical validation is required to confirm its real-world utility.
Gain of heterozygosity: an embryo-only, single-nucleotide polymorphism-based method to identify meiotic trisomies in preimplantation genetic testing for aneuploidy.
Hornak M, Brozek R, Musilova P … +4 more , Navratil R, Kubicek D, Travnik P, Vesela K
Reprod Biomed Online · 2026 Apr · PMID 42134026 · Publisher ↗
RESEARCH QUESTION: Can gain of heterozygosity (GOH) measured from embryo single- nucleotide polymorphism (SNP) data reliably identify meiotic trisomies during PGT-A without parental DNA samples? DESIGN: Retrospective sin...
RESEARCH QUESTION: Can gain of heterozygosity (GOH) measured from embryo single- nucleotide polymorphism (SNP) data reliably identify meiotic trisomies during PGT-A without parental DNA samples? DESIGN: Retrospective single-centre laboratory study using de-identified trophectoderm biopsy data from a combined monogenic disorder and aneuploidy testing programme. After whole-genome amplification and SNP-array genotyping, chromosomes were divided into bins of approximately 150 heterozygous markers using a euploid reference panel. The GOH was calculated as the relative increase in heterozygosity per bin; bins with 30% or more gain were considered GOH-positive, and chromosomes with three or more consecutive GOH-positive bins were classified as meiotic trisomies. Meiotic origin was verified by parental haplotype analysis (karyomapping). RESULTS: Among 209 meiotic trisomies (205 evaluable), GOH algorithm correctly classified 200, yielding a sensitivity of 97.6%. Misclassifications occurred mainly on small chromosomes with limited GOH coverage; one occurred in an embryo from a consanguineous union with reduced heterozygosity. In the clinical cohort of 1261 blastocysts (301 IVF cycles; mean maternal age 34.2 years), 63.6% were euploid, 29.9% uniformly aneuploid and 6.5% mosaic. The GOH analysis identified 200 meiotic trisomies and five meiotic triploids. The GOH-positive regions showed a 45.6% increase in heterozygous SNPs compared with diploid baseline, and spanned, on average, 74.1% of the trisomic chromosome length. Among 410 chromosome-error events, 89% arose from maternal meiosis; in mosaic embryos, parental contributions were balanced. CONCLUSIONS: GOH provides an embryo-only, SNP-based method to classify trisomies (meiotic versus mitotic) as an add-on to standard copy number variations/B-allele frequency assessment, without requiring parental DNA. This added mechanistic resolution may reduce clinically relevant misclassification of trisomies.
Diet in assisted reproductive technology: what should we recommend? A systematic review from current evidence to tailored nutritional approaches for enhancing reproductive success.
Fabozzi G, Conforti A, Abodi M … +15 more , Balò V, Bordignon E, Canichella S, Cantatore C, Cutini M, Deleuse M, De Maio F, De Toni L, Laguzzi FM, Pagliaroli E, Trabucco E, Turcatel I, Volanti V, Gennarelli G, Specialist Interest Group ‘Nutrition and Reproduction’ of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR)
Reprod Biomed Online · 2026 Feb · PMID 42119548 · Publisher ↗
Over recent years, nutrition has been increasingly recognized as a modifiable factor influencing fertility and the outcomes of assisted reproductive technology (ART). Preconception dietary habits in both sexes affect bod...
Over recent years, nutrition has been increasingly recognized as a modifiable factor influencing fertility and the outcomes of assisted reproductive technology (ART). Preconception dietary habits in both sexes affect body weight, metabolic health and the chances of achieving pregnancy. To systematically review the current evidence on the role of diet in ART, a systematic search was conducted in PubMed, Web of Science and Embase up to February 2025. Eligible studies included peer-reviewed clinical research assessing dietary interventions in couples undergoing ART. A total of 39 original studies were included. Findings suggest that adherence to healthy dietary patterns improves ART outcomes. Consistent effects on live birth, however, have not been demonstrated. Conversely, unhealthy patterns, notably the Western diet, are associated with poorer outcomes. Evidence for exclusion diets or specific nutrients is inconclusive, with potential benefits observed only in selected subgroups, such as women with polycystic ovary syndrome or coeliac disease. In conclusion, no single dietary approach is proven to enhance IVF success, nor is macronutrient exclusion supported. Personalized dietary strategies, including tailored nutrition, micronutrient supplementation and precision probiotics, are needed to address gut dysbiosis and metabolic disturbances, thereby improving ART outcomes and supporting long-term reproductive health.
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