Human reproduction openPub Date : 2026-02-17eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag014
Mujin Ye, Mariana Tavares Barroso, Anna Sara Oberg, Nermin Hadziosmanovic, Arturo Reyes Palomares, Kenny A Rodriguez-Wallberg
{"title":"First trimester growth after fresh or frozen single embryo transfer: embryo cleavage vs blastocyst stages.","authors":"Mujin Ye, Mariana Tavares Barroso, Anna Sara Oberg, Nermin Hadziosmanovic, Arturo Reyes Palomares, Kenny A Rodriguez-Wallberg","doi":"10.1093/hropen/hoag014","DOIUrl":"10.1093/hropen/hoag014","url":null,"abstract":"<p><strong>Study question: </strong>Is first-trimester intrauterine growth different between pregnancies resulting in live births established using fresh or frozen single embryo transfers (ET), and is it related to the embryo stage at the timing of transfer?</p><p><strong>Summary answer: </strong>Among pregnancies resulting in live birth, the use of frozen embryo transfer was associated with larger crown-rump length in the first trimester compared with fresh embryo transfer, regardless of the embryo stage at the timing of transfer.</p><p><strong>What is known already: </strong>Studies have indicated that singletons born following frozen/thawed ET have a higher likelihood of increased birthweight, in comparison with children born after fresh ET. A few studies have also suggested greater crown-rump length (CRL) in pregnancies after frozen embryo transfer (FET) compared to fresh ET. However, discrepancies exist regarding the intrauterine growth between fresh ET and FET groups, and the knowledge regarding the effect of embryo stage at transfer (cleavage stage vs. blastocyst stage) on the first-trimester growth remains limited.</p><p><strong>Study design size duration: </strong>This prospective cohort study included all single ETs resulting in singleton pregnancies and live births following either FET or fresh ET at an academic reproductive medical center during 2013-2024.</p><p><strong>Participants/materials setting methods: </strong>Among 3445 singleton live births during the study period, 54.3% were after FET, and 62.2% after blastocyst transfer. All underwent an ultrasound scan between 6 and 12 gestational weeks to measure the CRL (mm). Generalized additive models were used to compare the CRL between pregnancies after FET and fresh ET, as well as to investigate associations according to embryo stage at transfer (cleavage stage or blastocyst stage), accounting for multiple confounders.</p><p><strong>Main results and the role of chance: </strong>Compared with pregnancies after fresh ET, the CRL in pregnancies after FET was larger after adjusting for gestational age, embryo stage at transfer, parental age, maternal BMI, and smoking status in the first trimester, though the difference was small (β = 0.30 mm, 95% CI: 0.00-0.60, <i>P </i>= 0.053). The difference remained in subgroups defined by the embryo stage at the timing of transfer (β = 0.31 mm, 95% CI: -0.01-0.62, <i>P </i>= 0.055 and β = 0.22 mm, 95% CI: 0.06-0.39, <i>P </i>= 0.008 for cleavage and blastocyst stage, respectively). Normalizing CRL to a reference population conceived naturally from the INTERGROWTH-21(st) project showed that the mean CRL <i>Z</i>-scores in pregnancies after fresh ET and FET were both greater than 0 before day 63, suggesting the CRL in the present study population was larger than that of the non-ART population.</p><p><strong>Limitations reasons for caution: </strong>The lack of adjustment for other relevant confounders, such as maternal infertility factors, could lea","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag014"},"PeriodicalIF":8.6,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-02-17eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag013
Dingmin Yan, Yuedong Wang, Xishi Liu, Sun-Wei Guo
{"title":"Impaired PIEZO1 function drives uterine hypercontractility in adenomyosis-associated dysmenorrhea.","authors":"Dingmin Yan, Yuedong Wang, Xishi Liu, Sun-Wei Guo","doi":"10.1093/hropen/hoag013","DOIUrl":"10.1093/hropen/hoag013","url":null,"abstract":"<p><strong>Study question: </strong>Does PIEZO1 play any role in adenomyosis-associated dysmenorrhea?</p><p><strong>Summary answer: </strong>PIEZO1 downregulation in the myometrium reduces the expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production, leading to increased and irregular contractility that contributes to dysmenorrhea in women with adenomyosis.</p><p><strong>What is known already: </strong>Aberrant uterine contractility has long been documented in women with adenomyosis, but our knowledge of the molecular mechanisms governing uterine contractility is quite limited. Oxytocin receptor (OTR) expression in myometrium is elevated and correlates with uterine contractile amplitude and the severity of dysmenorrhea in women with adenomyosis. Adenomyosis induced in mice leads to increased uterine contractile amplitude and irregularity, accompanied by progressive generalized hyperalgesia. Additionally, increased myometrial vasopressin receptor (VP1αR) and potentially prostaglandin F2α (PGF<sub>2α</sub>) may also contribute to uterine hyperactivity.</p><p><strong>Study design size and duration: </strong>After written informed consent, we collected myometrial tissues ipsilateral and contralateral to adenomyotic lesions from 30 patients with adenomyosis (AM). As controls, normal myometrial tissue samples (CTL) were procured from 20 cycling women free of endometriosis and adenomyosis, age- and menstrual phase-matched with the AM group. Additionally, primary myometrial smooth muscle cells (SMCs) derived from 15 each AM and CTL subjects, age- and menstrual phase-matched, were cultured for gene and protein expression quantification and <i>in vitro</i> experimentation. In addition, 64 female Balb/C mice were randomly assigned in equal sizes to AM and CTL groups, with mice in the AM group receiving an AM induction procedure. Every 4-weeks post-induction until the 12th week, eight mice from each group were sacrificed, and their myometrial tissues were harvested. Uterine horn tissues were harvested and processed for histochemistry, immunohistochemistry (IHC), and Masson trichrome staining.</p><p><strong>Participants/materials setting and methods: </strong>We performed Masson trichrome staining and IHC analysis of PIEZO1, PIEZO2, OTR, eNOS, phosphorylated eNOS (p-eNOS), and iNOS on myometrial tissue samples from AM and CTL groups. Western blotting analyses were performed to evaluate the protein expression levels of eNOS, p-eNOS, and iNOS in myometrial SMCs, and the concentration of NO metabolite was quantitated. Real-time RT-PCR and western-blotting analyses were performed to evaluate the gene and protein expression levels of PIEZO1, PIEZO2, and OTR under different substrate stiffness. The gene and protein expression levels of eNOS (and p-eNOS for protein) and iNOS were also evaluated after treatment of myometrial SMCs with PIEZO1 agonist Yoda1 and antagonist Dooku1, with or without non-selective NOS inhibitor L-NAME and sele","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag013"},"PeriodicalIF":8.6,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-02-17eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag012
Nam T Nguyen, Vu N A Ho, Toan D Pham, Minh H N Nguyen, Duy L Nguyen, Ho L Le, Khanh T Q Le, Luong D Ly, Mai T N Tran, Tuong M Ho, Robert J Norman, Lan N Vuong
{"title":"Impact of glucose metabolism abnormalities on live birth rate in South-East Asian women with polycystic ovary syndrome.","authors":"Nam T Nguyen, Vu N A Ho, Toan D Pham, Minh H N Nguyen, Duy L Nguyen, Ho L Le, Khanh T Q Le, Luong D Ly, Mai T N Tran, Tuong M Ho, Robert J Norman, Lan N Vuong","doi":"10.1093/hropen/hoag012","DOIUrl":"10.1093/hropen/hoag012","url":null,"abstract":"<p><strong>Study question: </strong>Is there a difference in live birth rates at 24 months between infertile women with polycystic ovary syndrome (PCOS) who have normal versus abnormal glucose metabolism?</p><p><strong>Summary answer: </strong>Abnormal glucose metabolism did not significantly reduce live birth rates but was associated with increased obstetric complications.</p><p><strong>What is known already: </strong>Women with PCOS are often at increased risk of glucose metabolism disorders. However, evidence about the impact of these disorders on pregnancy outcomes remains limited, particularly in Asian populations.</p><p><strong>Study design size duration: </strong>This prospective cohort study was conducted at a reproductive care centre in Vietnam from June 2020 to August 2024. A total of 1208 women were enrolled.</p><p><strong>Participants/materials setting methods: </strong>Eligible participants were infertile women aged 18-40 years diagnosed with PCOS (Rotterdam criteria). Comprehensive assessments included medical history, anthropometric measurements, endocrine evaluations, fasting plasma glucose (FPG), glycosylated haemoglobin (HbAlc), and oral glucose tolerance tests (OGTT). Participants were categorized into normal or abnormal glucose metabolism groups and monitored for live birth outcomes at 24 months from the first visit.</p><p><strong>Main results and the role of chance: </strong>Live birth rates at 24 months were comparable between women with normal versus abnormal glucose metabolism (52.7% vs 48.2%, <i>P</i> = 0.12). However, obstetric complications, including gestational diabetes mellitus (15.2% vs 28.0%, <i>P</i> < 0.001) and hypertensive disorders of pregnancy (2.3% vs 9.0%, <i>P</i> < 0.001), were more common in the group with abnormal glucose metabolism. In women who conceived naturally, greater waist circumference and higher Homeostatic Model Assessment of Insulin Resistance index were significantly associated with lower odds of live birth, whereas the presence of hyperandrogenism was associated with higher odds of live birth. No factors were significantly associated with live birth in the group that conceived via ovulation induction plus IUI. In the group that conceived through IVF or IVM, a higher BMI was significantly associated with a lower live birth rate.</p><p><strong>Limitations reasons for caution: </strong>This single-centre study was conducted exclusively on infertile women from South-East Asia who had PCOS, potentially limiting generalizability to other populations. Additionally, metabolic assessments were only performed at baseline, preventing evaluation of longitudinal changes and their dynamic effects on reproductive outcomes.</p><p><strong>Wider implications of the findings: </strong>While no significant difference in live birth rates was observed between PCOS women with normal and abnormal glucose metabolism, the abnormal glucose metabolism group experienced higher rates of gestational complications. These","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag012"},"PeriodicalIF":8.6,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-02-13eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag010
Paula Cots-Rodríguez, Xinyin Wang, Mirian Sanchez-Tudela, Karen K Siu, Patrick Yip, Emilio Gómez, Jeffrey E Lee, Julieta G Hamze, Maria Jiménez-Movilla
{"title":"JUNO-coated beads as a functional assay to capture and characterize fertilization-competent human sperm.","authors":"Paula Cots-Rodríguez, Xinyin Wang, Mirian Sanchez-Tudela, Karen K Siu, Patrick Yip, Emilio Gómez, Jeffrey E Lee, Julieta G Hamze, Maria Jiménez-Movilla","doi":"10.1093/hropen/hoag010","DOIUrl":"10.1093/hropen/hoag010","url":null,"abstract":"<p><strong>Study question: </strong>Can human fertilization-competent spermatozoa be captured through their ability to bind the oocyte receptor JUNO?</p><p><strong>Summary answer: </strong>JUNO-coated beads, which mimic the oocyte geometry, selectively bound acrosome-reacted spermatozoa with intact DNA, revealing that vitrification preserves functional sperm binding while slow cryopreservation increases non-specific interactions.</p><p><strong>What is known already: </strong>It is well established that sperm must undergo the acrosome reaction and expose the receptor IZUMO1 on the sperm head to bind specifically to JUNO on the oolemma. Studying the spermatozoa that reaches and engages with the oolemma, however, remains highly challenging due to the technical difficulty of recovering these sperm at the site of the molecular interaction. Bead-based models that contain oocyte receptors have therefore emerged as a powerful approach to functionally assess sperm-oocyte interactions, with promising applications for evaluating sperm quality.</p><p><strong>Study design size duration: </strong>This was a cross-sectional experimental study including 21 semen donors of reproductive age recruited between January 2023 and June 2025. The JUNO-bead-based model was first validated using fresh human semen samples to establish the optimal sperm concentration and co-incubation time. Subsequently, two semen preservation methods, slow freezing and rapid freezing, were compared with respect to sperm-binding capacity to JUNO-coated beads, acrosomal status and DNA integrity. Finally, donors were classified according to sperm-binding capacity and validated by the hamster test.</p><p><strong>Participants/materials setting methods: </strong>Recombinant JUNO protein was secreted and purified from <i>Drosophila melanogaster</i> S2 cultures. Digital SPR was used to confirm JUNO-IZUMO1 binding kinetics and imaging flow cytometry was performed to assess the biological activity of recombinant JUNO. Protein-bead conjugation and activity were verified by immunochemistry and western blot. Human semen samples were obtained from donors aged 19-42 years, including both fresh ejaculates and cryopreserved samples. Sperm-binding capacity, acrosome reaction, and DNA fragmentation were analysed using widefield fluorescence microscopy and flow cytometry, and the specificity of sperm-bead interaction was evaluated with anti-IZUMO1 monoclonal antibodies.</p><p><strong>Main results and the role of chance: </strong>Recombinant JUNO bind human IZUMO1 ectodomain with a KD = 38 nM and specifically recognizes acrosome-reacted sperm and not acrosome-intact sperm. Human JUNO recombinant protein was successfully conjugated to oocyte-sized beads to generate a sperm-binding assay mimicking the geometry of the oocyte and experimental conditions of IVF. Human sperm bound specifically to JUNO-beads in a dose- and time-dependent manner, with highly significant differences compared to control beads (<i>P </i>≤","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoag010"},"PeriodicalIF":8.6,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lack of difference in thyroid hormone profile between offspring conceived naturally and through ART.","authors":"Yiyuan Zhang, Yifei Sun, Ting Lan, Huang Wei, Wenjing Wan, Linlin Cui, Wei Zhou, Zi-Jiang Chen","doi":"10.1093/hropen/hoag009","DOIUrl":"10.1093/hropen/hoag009","url":null,"abstract":"<p><strong>Study question: </strong>Does the thyroid function of children conceived through ART differ from that of naturally conceived (NC) children?</p><p><strong>Summary answer: </strong>Our study results indicate that both children conceived through fresh embryo transfer and frozen embryo transfer exhibit a thyroid function profile similar to that of NC children.</p><p><strong>What is known already: </strong>Few studies have compared thyroid function between ART-conceived and NC children, and conflicting conclusions have been reported.</p><p><strong>Study design size duration: </strong>This study was based on a cohort at a tertiary health centre in China. The prospective cohort study included 9450 children born between 2005 and 2021 and followed up until June 2023. The outcomes of interest were the levels of the children's thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin autoantibody (A-TG), and thyroid peroxidase antibody (A-TPO).</p><p><strong>Participants/materials setting methods: </strong>The participants were 3940 fresh embryo transfer conceived children (ET group), 4730 frozen embryo transfer conceived children (FET group), and 780 NC children. Their ages ranged from 1.5 to 10 years. Generalized estimating equations (GEE) was used to compare the main outcomes.</p><p><strong>Main results and the role of chance: </strong>No significant between-group differences were observed in FT4 levels or the odds of TSH, FT3, FT4, A-TG, or A-TPO levels beyond the standard range. Further subgroup analysis indicated that the ET group exhibited a slightly higher TSH level than the NC group during the toddler age period (mean TSH: 2.93 vs. 2.72 µIU/ml). However, this difference was no longer significant among preschool and school-aged children. Additionally, there were no significant differences in FT4 levels between the ART and NC groups across all age subgroups.</p><p><strong>Limitations reasons for caution: </strong>Due to the inability to acquire urinary iodine data, we cannot adequately assess the influence of iodine intake on the study results. Both the unavoidable loss to follow-up in the cohort and the imbalance in the proportion of girls (higher in the NC group than in the ART group) may potentially introduce selection bias.</p><p><strong>Wider implications of the findings: </strong>The study results indicate that ART-conceived children exhibit a thyroid function profile comparable to that of NC children. Furthermore, ART appears to be safe for long-term thyroid function in children.</p><p><strong>Study funding/competing interests: </strong>National Key Research and Development Program of China (no. 2024YFC2706700), the National Natural Science Foundation of China (NSFC) Regional Innovation and Development Joint Fund (U24A20664), the National Key Technology Research and Developmental Program of China (2024YFC2706902), CAMS Innovation Fund for Medical Sciences (2021-I2M-5-001), National Special S","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoag009"},"PeriodicalIF":8.6,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-02-02eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag004
Norbert Gleicher, Sonia Gayete-Lafuente, Lara Guijarro-Baude, Pasquale Patrizio, David F Albertini, David H Barad
{"title":"The declining efficiency of IVF in the USA.","authors":"Norbert Gleicher, Sonia Gayete-Lafuente, Lara Guijarro-Baude, Pasquale Patrizio, David F Albertini, David H Barad","doi":"10.1093/hropen/hoag004","DOIUrl":"10.1093/hropen/hoag004","url":null,"abstract":"<p><strong>Study question: </strong>Has the efficiency of IVF cycles in the USA declined between 2012 and 2021?</p><p><strong>Summary answer: </strong>National U.S. data show a continuous linear decline in IVF cycle efficiency between 2012 and 2021.</p><p><strong>What is known already: </strong>Previous studies reported that live birth rates after IVF increased until 2010 but subsequently declined, potentially due to the introduction of IVF 'add-ons' and changes in clinical practice.</p><p><strong>Study design size duration: </strong>Retrospective cohort study, using publicly available national U.S. IVF outcome data reported annually to the Centers for Disease Control and Prevention (CDC) for the period 2012-2021.</p><p><strong>Participants/materials setting methods: </strong>CDC annual reports were used as a data source. Extracted variables included a number of IVF cycle starts, embryo transfers, embryo banking cycles, and live births. IVF 'treatment efficiency' was calculated as the proportion of live births per initiated cycle (intent-to-treat analysis).</p><p><strong>Main results and the role of chance: </strong>Over the study period, IVF cycle starts increased by 234.7% (176 274 to 413 776), embryo transfers by 150.3% (134 471 to 202 121), and embryo banking cycles by 902.3% (18 585 to 167 689). Live births increased by 179.2% (51 286 to 91 906). However, cycle efficiency declined from 29.1% in 2012 to 22.2% in 2021, a relative reduction of 23.4%, with an approximately linear decline across the decade.</p><p><strong>Limitations reasons for caution: </strong>The study is based on aggregate CDC data without patient-level granularity. Therefore, analyses could not control for confounding factors such as parity, infertility diagnosis, or detailed age subgroups. Embryo banking practices also complicate year-to-year comparisons of live birth rates.</p><p><strong>Wider implications of the findings: </strong>These findings suggest that despite substantial growth in IVF cycle numbers, treatment efficiency has progressively declined in the USA over the last decade. This decline coincided with a rapid increase in the use of embryo banking and other IVF 'add-ons'. The results raise concern about current clinical practices and highlight the need for critical re-evaluation of routine interventions in IVF.</p><p><strong>Study funding/competing interests: </strong>No external funding was received for this study. NG and DHB hold patents related to androgen treatment in females (DHEA) with numbers US8067400B2, US8501718B2, and US9375436B2 (listed in USPTO/public records and assigned to American Infertility of New York). They also receive royalties from Nutraceuticals LLC, which has helped commercialize DHEA as a nutritional supplement.</p><p><strong>Trial registration number: </strong>N/A.</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoag004"},"PeriodicalIF":11.1,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-01-30eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag007
Kentaro Iga
{"title":"Non-significant results do not imply similarity or safety in NC-FET follicle-size comparisons: a clarification.","authors":"Kentaro Iga","doi":"10.1093/hropen/hoag007","DOIUrl":"10.1093/hropen/hoag007","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoag007"},"PeriodicalIF":8.6,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12906230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-01-30eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag008
Jie Zhang, Ling Wu
{"title":"Reply: non-significant results do not imply similarity or safety in NC-FET follicle-size comparisons: a clarification.","authors":"Jie Zhang, Ling Wu","doi":"10.1093/hropen/hoag008","DOIUrl":"10.1093/hropen/hoag008","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoag008"},"PeriodicalIF":11.1,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12906229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-01-25eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag005
Stefano Palomba, Flavia Costanzi, Giuseppe Seminara, Donatella Caserta, Antonio Aversa
{"title":"Is polycystic ovary syndrome associated with uterine malformations? A systematic review using Bradford Hill's causality framework.","authors":"Stefano Palomba, Flavia Costanzi, Giuseppe Seminara, Donatella Caserta, Antonio Aversa","doi":"10.1093/hropen/hoag005","DOIUrl":"10.1093/hropen/hoag005","url":null,"abstract":"<p><strong>Study question: </strong>Is there a causal relationship between polycystic ovary syndrome (PCOS) and the occurrence of congenital uterine anomalies (CUAs)?</p><p><strong>Summary answer: </strong>Bradford Hill criteria did not support the causal relationship between PCOS and CUAs.</p><p><strong>What is known already: </strong>PCOS and CUAs are both linked to infertility and complications during pregnancy, but it is unclear whether PCOS increases the risk of developing CUAs.</p><p><strong>Study design size duration: </strong>A systematic review with qualitative analysis using Bradford Hill criteria was performed.</p><p><strong>Participants/materials setting methods: </strong>Studies evaluating CUAs in women with PCOS or mechanisms linking PCOS-related factors to Müllerian development were selected. Comprehensive searches were conducted in MEDLINE, Web of Science, Cochrane Library, and Scopus for studies published in English from 1 January 2000 up to 30 August 2025 using terms related to PCOS, CUAs, and Müllerian anomalies. The nine Bradford Hill criteria were applied using modern epidemiological tools and concepts. For each Bradford Hill criterion, we prioritized studies according to the highest available level of evidence as defined by the Oxford Centre for Evidence-Based Medicine (CEBM). Study quality and risk of bias were systematically assessed using validated tools appropriate to each study design.</p><p><strong>Main results and the role of chance: </strong>Twenty-one studies were included (5 systematic reviews with meta-analysis, 4 case-control, 11 cohort, 1 cross-sectional). Evidence supported the Bradford Hill criteria of biological gradient, coherence, plausibility, and analogy, whereas consistency, specificity, temporality, and experimental evidence were not met, and the strength of association only partially fulfilling. Overall, the findings provide weak qualitative support for a potential causal relationship between PCOS and CUAs.</p><p><strong>Limitations reasons for caution: </strong>Findings are limited by heterogeneity in diagnostic criteria and imaging methods, and potential selection bias. In addition, the strength of association is characterized by large coefficient interval and modest significance.</p><p><strong>Wider implications of the findings: </strong>Routine uterine imaging for identifying/screening CUAs is not justified by the PCOS diagnosis alone until standardized prospective studies demonstrate a causal inference between diseases.</p><p><strong>Study funding/competing interests: </strong>Departmental funds (Departments of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, and of Experimental and Clinical Medicine of 'Magna Graecia', University of Catanzaro; Italy) were used to support the authors throughout the study period and manuscript preparation. No specific external funding was received. The authors declare no competing interests.</p><p><strong>Registration number: </str","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoag005"},"PeriodicalIF":11.1,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12902784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-01-22eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag006
Subhadra Evans, David Skvarc, Adrian Esterman, Matthew I Mackay, Melissa O'Shea, Leesa Van Niekerk, Marilla L Druitt, Jim Tsaltas, Simon R Knowles, Elesha Parigi, Katherine Stanley, Jill Harris, Meg Barber, Madeleine Dober, Charlotte Dowding, Antonina Mikocka-Walus
{"title":"Telehealth cognitive behavioural therapy improves health-related quality of life and pain in endometriosis: the Healing Pelvic Pain Intervention (HaPPI)-a randomized controlled trial.","authors":"Subhadra Evans, David Skvarc, Adrian Esterman, Matthew I Mackay, Melissa O'Shea, Leesa Van Niekerk, Marilla L Druitt, Jim Tsaltas, Simon R Knowles, Elesha Parigi, Katherine Stanley, Jill Harris, Meg Barber, Madeleine Dober, Charlotte Dowding, Antonina Mikocka-Walus","doi":"10.1093/hropen/hoag006","DOIUrl":"10.1093/hropen/hoag006","url":null,"abstract":"<p><strong>Study question: </strong>Is telehealth cognitive behavioural therapy (CBT) or yoga effective in improving health-related quality of life (HRQoL) and secondary outcomes for endometriosis?</p><p><strong>Summary answer: </strong>Endometriosis-tailored CBT is superior to education for improving HRQoL and pain.</p><p><strong>What is known already: </strong>Endometriosis is a burdensome disease that contributes to diminished quality of life. Current biomedical care including hormonal and analgesic treatment is associated with inconsistent efficacy. Interdisciplinary care is therefore needed to augment the well-being of people with endometriosis. Although studies have suggested that CBT and yoga are promising for relieving pain and other symptoms associated with endometriosis, the evidence remains limited because they are based on small pilot studies.</p><p><strong>Study design size duration: </strong>In this parallel 8-week randomized controlled trial (RCT), 334 participants were randomized using a computer-generated sequence with allocation concealment between April 2021 and February 2024. Outcome assessors were blinded to the group.</p><p><strong>Participants/materials setting methods: </strong>Participants required a diagnosis of endometriosis with pain for at least 6 months, and access to internet. Participants were randomly allocated to: (i) CBT (8-week telehealth therapist-led group, n = 79); (ii) yoga (8-week telehealth therapist-led group, n = 83); or (iii) education materials via email (n = 84). Primary outcomes: endometriosis-specific HRQoL (Endometriosis Health Profile-30; EHP-30 Total and Pain); general HRQoL (EQ-5D-5L global health) at post-treatment (8 weeks). Secondary outcomes: pain (period pain, bowel pain, bladder pain, and sexual pain), pain catastrophizing, pain self-efficacy, psychological distress, sleep, fatigue, menstrual symptoms, and central sensitization. Mixed-effects models examined group by time differences.</p><p><strong>Main results and the role of chance: </strong>The CBT group reported statistically significant improvements in endometriosis-specific HRQoL (EHP Pain <i>β</i> = -0.58, 95% CI = -0.89, -0.26, <i>P</i> = 0.01), and general HRQoL (EQ-5D-5L global health <i>β</i> = 0.52, 95% CI = 0.21, 0.84, <i>P</i> = 0.02) compared to the education control group. CBT was also superior to education for pelvic pain (menstrual pain, bowel pain, bladder pain, and sexual pain), pain self-efficacy, and pain catastrophizing. Effect sizes for CBT were generally medium to large (Cohen's D = -0.28 to -0.93). Yoga was superior to education for menstrual symptoms and sexual pain, with medium effect sizes (Cohen's D = -0.56 to -0.71).</p><p><strong>Limitations reasons for caution: </strong>Due to the presence of COVID-19 restrictions during data collection, CBT and yoga were delivered online. As a result, it is unclear whether CBT and yoga would have the same effects if delivered face-to-face, or whether online delivery would","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoag006"},"PeriodicalIF":8.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}