Human reproduction open最新文献

{"title":"Use of mesenchymal stem cells to enhance or restore fertility potential: a systematic review of available experimental strategies.","authors":"L Cacciottola, F Vitale, J Donnez, M M Dolmans","doi":"10.1093/hropen/hoad040","DOIUrl":"10.1093/hropen/hoad040","url":null,"abstract":"<p><strong>Study question: </strong>To what extent does regenerative medicine with stem cell therapy help to address infertility issues for future clinical application?</p><p><strong>Summary answer: </strong>Regenerative medicine using different stem cell sources is yielding promising results in terms of protecting the ovarian reserve from damage and senescence, and improving fertility potential in various preclinical settings.</p><p><strong>What is known already: </strong>Regenerative medicine using stem cell therapy is emerging as a potential strategy to address a number of issues in the field of human reproduction. Indeed, different types of adult and fetal mesenchymal stem cells (MSCs) have been tested with promising results, owing to their ability to differentiate into different tissue lineages, move toward specific injured sites (homing), and generate a secretome with wound-healing, proangiogenic, and antioxidant capacities.</p><p><strong>Study design size duration: </strong>Guided by the checklist for preferred reporting items for systematic reviews and meta-analyses, we retrieved relevant studies from PubMed, Medline, and Embase databases until June 2023 using the following keywords: 'mesenchymal stem cells' AND 'ovarian follicles' OR 'ovarian tissue culture' OR 'ovarian follicle culture' OR 'cumulus oocyte complex'. Only peer-reviewed published articles written in English were included.</p><p><strong>Participants/materials setting methods: </strong>The primary outcome for the experimental strategies was evaluation of the ovarian reserve, with a focus on follicle survival, number, and growth. Secondary outcomes involved analyses of other parameters associated with the follicle pool, such as hormones and growth factors, ovarian tissue viability markers including oxidative stress levels, oocyte growth and maturation rates, and of course pregnancy outcomes.</p><p><strong>Main results and the role of chance: </strong>Preclinical studies exploring MSCs from different animal origins and tissue sources in specific conditions were selected (n = 112), including: <i>in vitro</i> culture of granulosa cells, ovarian tissue and isolated ovarian follicles; ovarian tissue transplantation; and systemic or intraovarian injection after gonadotoxic or age-related follicle pool decline. Protecting the ovarian reserve from aging and gonadotoxic damage has been widely tested <i>in vitro</i> and <i>in vivo</i> using murine models and is now yielding initial data in the first ever case series of patients with premature ovarian insufficiency. Use of MSCs as feeder cells in ovarian tissue culture was found to improve follicle outcomes and oocyte competence, bringing us one step closer to future clinical application. MSCs also have proved effective at boosting revascularization in the transplantation site when grafting ovarian tissue in experimental animal models.</p><p><strong>Limitations reasons for caution: </strong>While preclinical results look promising in te","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad040"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720958","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":"Enzymatic tissue processing after testicular biopsy in non-obstructive azoospermia enhances sperm retrieval.","authors":"V Vloeberghs, N De Munck, A Racca, I Mateizel, K Wouters, H Tournaye","doi":"10.1093/hropen/hoad039","DOIUrl":"10.1093/hropen/hoad039","url":null,"abstract":"<p><strong>Study question: </strong>What is the added value of enzymatic processing of testicular biopsies on testicular sperm retrieval (SR) rates for patients with non-obstructive azoospermia (NOA)?</p><p><strong>Summary answer: </strong>In addition to mechanical mincing, enzymatic digestion increased SR rates in testicular biopsies of NOA patients.</p><p><strong>What is known already: </strong>Many studies focus on the surgical approach to optimize recovery of testicular sperm in NOA, and in spite of that, controversy still exists about whether the type of surgery makes any difference as long as multiple biopsies are taken. Few studies, however, focus on the role of the IVF laboratory and the benefit of additional lab procedures, e.g. enzymatic digestion, in order to optimize SR rates.</p><p><strong>Study design size duration: </strong>This retrospective single-center cohort study included all patients who underwent their first testicular sperm extraction (TESE) by open multiple-biopsy method between January 2004 and July 2022. Only patients with a normal karyotype, absence of Y-q deletions and a diagnosis of NOA based on histology were included. The primary outcome was SR rate after mincing and/or enzymes. The secondary outcome was cumulative live birth (CLB) after ICSI with fresh TESE and subsequent ICSI cycles with frozen TESE.</p><p><strong>Participants/materials setting methods: </strong>Multiple biopsies were obtained from the testis, unilaterally or bilaterally, on the day of oocyte retrieval. Upon mechanical mincing, biopsies were investigated for 30 min; when no or insufficient numbers of spermatozoa were observed, enzymatic treatment was performed using Collagenase type IV. Multivariable regression analysis was performed to predict CLB per TESE by adjusting for the following confounding factors: male FSH level, female age, and requirement of enzymatic digestion to find sperm.</p><p><strong>Main results and the role of chance: </strong>We included 118 patients, of whom 72 (61.0%) had successful SR eventually. Spermatozoa were retrieved after mechanical mincing for 28 patients (23.7%; 28/118) or after additional enzymatic digestion for another 44 patients (37.2%; 44/118). Thus, of the 90 patients requiring enzymatic digestion, sperm were retrieved for 44 (48.9%). Male characteristics were not different between patients with SR after mincing or enzymatic digestion, in regard to mean age (34.5 vs 34.5 years), testis volume (10.2 vs 10.6 ml), FSH (17.8 vs 16.9 IU/l), cryptorchidism (21.4 vs 34.1%), varicocele (3.6 vs 4.6%), or histological diagnosis (Sertoli-cell only 53.6 vs 47.7%, maturation arrest 21.4 vs 38.6%, sclerosis/atrophy 25.0 vs 13.6%).Of the 72 patients with sperm available for ICSI, 23/72 (31.9%) achieved a live birth (LB) after the injection with fresh testicular sperm (and fresh or frozen embryo transfers). Of the remaining 49 patients without LB, 34 (69.4%) had supernumerary testicular sperm frozen. Of these 34 patients, ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad039"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489649","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":"In infertile women with subclinical hypothyroidism, with or without thyroid peroxidase antibodies, serum TSH during pregnancy follows preconception values and thyroid hormones remain stable.","authors":"C De Geyter, L Matt, I De Geyter, R Moffat, C Meier","doi":"10.1093/hropen/hoad038","DOIUrl":"10.1093/hropen/hoad038","url":null,"abstract":"<p><strong>Study question: </strong>How does subclinical hypothyroidism, defined in infertile women during preconception by thyroid-stimulating hormone (TSH) >2.5 or >4.5 mIU/l, with or without thyroid peroxidase antibodies (anti-TPO) >100 IU/ml, impact thyroid hormone levels during pregnancy and after birth?</p><p><strong>Summary answer: </strong>During pregnancy, TSH levels remain similar to those in preconception, even with supplementary thyroxine, whereas the serum levels of anti-TPO progressively decline.</p><p><strong>What is known already: </strong>Overt hypothyroidism impacts both pregnancy and offspring but randomized clinical trials and cohort studies failed to detect the benefit of treatment with thyroxine in cases with low-threshold TSH or with anti-TPO during pregnancy.</p><p><strong>Study design size duration: </strong>First, the prevalence and reproducibility of two candidate cut-off levels of subclinical hypothyroidism in a cohort of 177 infertile women was compared with 171 women not aiming for pregnancy. Second, the impact of distinct setpoints of TSH in preconception (with or without anti-TPO) was monitored during pregnancy in 87 previously infertile women by high-frequency monitoring of thyroid function. Both studies were carried out from 2007 to 2019.</p><p><strong>Participants/materials setting methods: </strong>Reproducibility and prevalence of subclinical hypothyroidism were examined in infertile women presenting in the fertility care unit of an academic institution. Women not aiming for pregnancy participated as controls. In both groups, TSH and anti-TPO were measured two times on different occasions. In addition, a group of previously infertile women with known preconception setpoints of TSH (with or without anti-TPO) were followed up prospectively throughout pregnancy and after birth. During pregnancy, serum was sampled weekly until Week 12, then monthly until delivery, and once after birth. Only cases with preconception TSH >4.5 mIU/l were supplemented with thyroxine. After collection of all samples, the serum levels of anti-TPO and the major thyroid hormones were measured. Prolactin with known fluctuations during pregnancy was used as reference.</p><p><strong>Main results and the role of chance: </strong>Measures of both TSH and anti-TPO at two different time points were accurate and reproducible. The odds of subclinical hypothyroidism in infertile women and controls were similar. During pregnancy, TSH closely followed preconception TSH levels, whereas serum levels of the thyroid hormones predominantly remained within or above (not below) the reference. Treatment of infertile women with preconception TSH >4.5 mIU/l with thyroxine resulted in higher free thyroxine (fT4) serum levels. The serum levels of anti-TPO declined as pregnancies evolved.</p><p><strong>Limitations reasons for caution: </strong>The numbers of participants both in the prevalence study and in pregnancy did not reach the <i>a priori</i> estimated num","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad038"},"PeriodicalIF":0.0,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10589916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49694837","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":"Double vitrification and warming does not compromise the chance of live birth after single unbiopsied blastocyst transfer.","authors":"S Makieva, M K Sachs, M Xie, A Velasco, S El-Hadad, D R Kalaitzopoulos, I Dedes, R Stiller, B Leeners","doi":"10.1093/hropen/hoad037","DOIUrl":"10.1093/hropen/hoad037","url":null,"abstract":"<p><strong>Study question: </strong>Does double vitrification and thawing of an embryo compromise the chance of live birth after a single blastocyst transfer?</p><p><strong>Summary answer: </strong>The live birth rate (LBR) obtained after double vitrification was comparable to that obtained after single vitrification.</p><p><strong>What is known already: </strong>Double vitrification-warming (DVW) is commonly practiced to accommodate surplus viable embryos suitable for transfer, to allow retesting of inconclusively diagnosed blastocysts in preimplantation genetic testing (PGT), and to circumvent limitations associated with national policies on embryo culture in certain countries. Despite its popularity, the evidence concerning the impact of DVW practice on ART outcomes is limited and lacking credibility. This is the first thorough investigation of clinical pregnancy and LBR following DVW in the case where the first round of vitrification occurred at the zygote stage and the second round occurred at the blastocyst stage in the absence of biopsy.</p><p><strong>Study design size duration: </strong>This is a retrospective observational analysis of n = 407 single blastocyst transfers whereby embryos created by IVF/ICSI were vitrified-warmed once (single vitrification-warming (SVW) n = 310) or twice (DVW, n = 97) between January 2017 and December 2021.</p><p><strong>Participants/materials setting methods: </strong>In the SVW group, blastocysts were vitrified on Day 5/6 and warmed on the day of embryo transfer (ET). In the DVW group, two pronuclear (2PN) zygotes were first vitrified-warmed and then re-vitrified on Day 5/6 and warmed on the day of ET. Exclusion criteria were ETs from PGT and vitrified-warmed oocyte cycles. All of the ETs were single blastocyst transfers performed at the University Hospital Zurich in Switzerland following natural or artificial endometrial preparation.</p><p><strong>Main results and the role of chance: </strong>The biochemical pregnancy rate, clinical pregnancy rate (CPR), and LBR were all comparable between the DVW and SVW groups. The CPR for DVW was 44.3% and for SVW it was 42.3% (<i>P</i> = 0.719). The LBR for DVW was 30.9% and for SVW it was 28.7% (<i>P</i> = 0.675). The miscarriage rate was additionally similar between the groups: 27.9% for DVW and 32.1% for SVW groups (<i>P</i> = 0.765).</p><p><strong>Limitations reasons for caution: </strong>The study is limited by its retrospective nature. Caution should be taken concerning interpretation of these findings in cases where DVW occurs at different stages of embryo development.</p><p><strong>Wider implications of the findings: </strong>The result of the present study on DVW procedure provides a framework for counselling couples on their chance of clinical pregnancy per warming cycle. It additionally provides confidence and reassurance to laboratory professionals in certain countries where national policies limit embryo culture strategies making DVW inevitable.</p><p><s","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad037"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241797","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":"Risk factors associated with monozygotic twinning in offspring conceived by assisted reproductive technology.","authors":"Na Chen, Jingyu Li, Yexing Li, Yiyuan Zhang, Jiarong Li, Jie Gao, Jingmei Hu, Linlin Cui, Zi-Jiang Chen","doi":"10.1093/hropen/hoad035","DOIUrl":"10.1093/hropen/hoad035","url":null,"abstract":"<p><strong>Study question: </strong>What are the factors influencing the occurrence of monozygotic (MZ) twins in offspring conceived by assisted reproductive technology (ART)?</p><p><strong>Summary answer: </strong>Parental ages, the transfer of fresh versus frozen embryos, and the grade of blastocysts are all related to MZ twinning in ART offspring.</p><p><strong>What is known already: </strong>Offspring conceived by ART have significantly increased risk of MZ twins, which may be due to the characteristics of the infertile population. The objective of this study was to explore the incidence of monozygotic (MZ) twins after ART and to clarify the risk factors for MZ twinning.</p><p><strong>Study design size duration: </strong>A total of 255 monozygotic twins were enrolled in this cohort study, and then matched with singletons at a ratio of 1:4 randomly (with 1020 in the control group). All offspring were conceived by single embryo transfer.</p><p><strong>Participants/materials setting methods: </strong>The collected data were divided into the following three aspects for analysis: characteristics of the infertile population, gamete or embryo manipulations, and factors related to embryo development.</p><p><strong>Main results and the role of chance: </strong>The incidence of MZ twins was 1.638% (255 out of 15 567 pregnancies after single embryo transfers). Compared to singleton births, a significantly lower rate of frozen embryo transfers (FET; 78.0% vs 86.1% <i>P</i> = 0.002) was seen amongst the MZ twins. Amongst fresh ETs, the rate of blastocyst transfers in the MZ twins group was higher compared to that in the control group (92.9% vs 75.4%, <i>P</i> = 0.005). We also found that certain grades of blastocysts in terms of trophectoderm (TE) development, inner cell mass + TE development and the classification of 'top-quality' embryos were associated with the incidence of MZ twinning (<i>P</i> = 0.025, <i>P</i> = 0.012, <i>P</i> = 0.020, respectively). Logistic regression analysis revealed that higher paternal age (odds ratio (OR) = 0.94, 95% CI = 0.89-1.00, <i>P</i> = 0.029) and FET (OR = 0.48, 95% CI = 0.33-0.68, <i>P</i> = 0.001) may be protective factors against MZ twinning. However, higher maternal age (OR = 1.07, 95% CI = 1.01-1.13, <i>P</i> = 0.027) and the transfer of blastocysts (OR = 4.31, 95% CI = 1.46-12.73, <i>P</i> = 0.008) appeared to be associated with an increased risk of MZ twinning. Amongst blastocyst transfers, a C grade TE may be protective factor against MZ twinning (B: OR = 1.90, 95% CI = 1.18-3.07, <i>P</i> = 0.009; A: OR = 1.58, 95% CI = 0.93-2.67, <i>P</i> = 0.089).</p><p><strong>Limitations reasons for caution: </strong>First, our definition of MZ twins was based on twins' birth after single embryo transfers (SET), rather than ultrasound examination during early pregnancy. Second, the parental characteristics of the two groups were homogenous, so it was difficult to find any associations between infertility factors and the ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad035"},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10570986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241798","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":"Embryo selection through artificial intelligence versus embryologists: a systematic review.","authors":"M Salih, C Austin, R R Warty, C Tiktin, D L Rolnik, M Momeni, H Rezatofighi, S Reddy, V Smith, B Vollenhoven, F Horta","doi":"10.1093/hropen/hoad031","DOIUrl":"10.1093/hropen/hoad031","url":null,"abstract":"<p><strong>Study question: </strong>What is the present performance of artificial intelligence (AI) decision support during embryo selection compared to the standard embryo selection by embryologists?</p><p><strong>Summary answer: </strong>AI consistently outperformed the clinical teams in all the studies focused on embryo morphology and clinical outcome prediction during embryo selection assessment.</p><p><strong>What is known already: </strong>The ART success rate is ∼30%, with a worrying trend of increasing female age correlating with considerably worse results. As such, there have been ongoing efforts to address this low success rate through the development of new technologies. With the advent of AI, there is potential for machine learning to be applied in such a manner that areas limited by human subjectivity, such as embryo selection, can be enhanced through increased objectivity. Given the potential of AI to improve IVF success rates, it remains crucial to review the performance between AI and embryologists during embryo selection.</p><p><strong>Study design size duration: </strong>The search was done across PubMed, EMBASE, Ovid Medline, and IEEE Xplore from 1 June 2005 up to and including 7 January 2022. Included articles were also restricted to those written in English. Search terms utilized across all databases for the study were: ('Artificial intelligence' OR 'Machine Learning' OR 'Deep learning' OR 'Neural network') AND ('IVF' OR '<i>in vitro</i> fertili*' OR 'assisted reproductive techn*' OR 'embryo'), where the character '*' refers the search engine to include any auto completion of the search term.</p><p><strong>Participants/materials setting methods: </strong>A literature search was conducted for literature relating to AI applications to IVF. Primary outcomes of interest were accuracy, sensitivity, and specificity of the embryo morphology grade assessments and the likelihood of clinical outcomes, such as clinical pregnancy after IVF treatments. Risk of bias was assessed using the Modified Down and Black Checklist.</p><p><strong>Main results and the role of chance: </strong>Twenty articles were included in this review. There was no specific embryo assessment day across the studies-Day 1 until Day 5/6 of embryo development was investigated. The types of input for training AI algorithms were images and time-lapse (10/20), clinical information (6/20), and both images and clinical information (4/20). Each AI model demonstrated promise when compared to an embryologist's visual assessment. On average, the models predicted the likelihood of successful clinical pregnancy with greater accuracy than clinical embryologists, signifying greater reliability when compared to human prediction. The AI models performed at a median accuracy of 75.5% (range 59-94%) on predicting embryo morphology grade. The correct prediction (Ground Truth) was defined through the use of embryo images according to post embryologists' assessment following local respect","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 3","pages":"hoad031"},"PeriodicalIF":0.0,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10426717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10076934","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":"Cancer risk in children, adolescents, and young adults conceived by ART in 1983-2011.","authors":"Mandy Spaan, Martina Pontesilli, Alexandra W van den Belt-Dusebout, Curt W Burger, Marry M van den Heuvel-Eibrink, Anita C J Ravelli, Mariëtte Goddijn, Cornelis B Lambalk, Tessa J Roseboom, Flora E van Leeuwen","doi":"10.1093/hropen/hoad027","DOIUrl":"10.1093/hropen/hoad027","url":null,"abstract":"<p><strong>Study question: </strong>Do children, adolescents, and young adults born after ART, including IVF, ICSI and frozen-thawed embryo transfer (FET), have an increased risk of cancer compared with children born to subfertile couples not conceived by ART and children from the general population?</p><p><strong>Summary answer: </strong>After a median follow-up of 18 years, the overall cancer risk was not increased in children conceived by ART, but a slight risk increase was observed in children conceived after ICSI.</p><p><strong>What is known already: </strong>There is growing evidence that ART procedures could perturb epigenetic processes during the pre-implantation period and influence long-term health. Recent studies showed (non-)significantly increased cancer risks after ICSI and FET, but not after IVF.</p><p><strong>Study design size duration: </strong>A nationwide historical cohort study with prospective follow-up was carried out, including all live-born offspring from women treated with ART between 1983 and 2011 and subfertile women not treated with ART in one of the 13 Dutch IVF clinics and two fertility centers.</p><p><strong>Participants/materials setting methods: </strong>Children were identified through the mothers' records in the Personal Records Database. Information on the conception method of each child was collected through the mother's medical record. In total, the cohort comprises 89 249 live-born children of subfertile couples, of whom 51 417 were conceived using ART and 37 832 were not (i.e. conceived naturally, through ovulation induction, or after IUI). Cancer incidence was ascertained through linkage with the Netherlands Cancer Registry for the period 1989-2019. Cancer risk in children conceived using ART was compared with risk in children born to subfertile couples but not conceived by ART (hazard ratio (HR)) and children from the general population (standardized incidence ratios (SIRs)).</p><p><strong>Main results and the role of chance: </strong>In total, 358 cancers were observed after a median follow-up of 18 years. Overall cancer risk was not increased in children conceived using ART, when compared with the general population (SIR = 0.96, 95% CI = 0.81-1.12) or with children from subfertile couples not conceived by ART (HR = 1.06, 95% CI = 0.84-1.33). Compared with children from subfertile couples not conceived by ART, the use of IVF or FET was not associated with increased cancer risk, but ICSI was associated with a slight risk increase (HR = 1.58, 95% CI = 1.08-2.31). Risk of cancer after ART did not increase at older ages (≥18 years, HR = 1.26, 95% CI = 0.88-1.81) compared to cancer risk in children not conceived by ART.</p><p><strong>Limitations reasons for caution: </strong>The observed increased risk among children conceived using ICSI must be interpreted with caution owing to the small number of cases.</p><p><strong>Wider implications of the findings: </strong>After a median follow-up of 18 years, children","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 3","pages":"hoad027"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/36/hoad027.PMC10279651.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9710260","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":"Measurement of changes in uterine and fibroid volume during treatment of heavy menstrual bleeding (HMB).","authors":"K Yin, L Whitaker, E Hojo, S McLenachan, J Walker, G McKillop, C Stubbs, L Priest, M Cruz, N Roberts, H Critchley","doi":"10.1093/hropen/hoad021","DOIUrl":"10.1093/hropen/hoad021","url":null,"abstract":"<p><strong>Study question: </strong>Does application of an unbiased method for analysis of magnetic resonance (MR) images reveal any effect on uterine or fibroid volume from treatment of heavy menstrual bleeding (HMB) with three 12-week courses of the selective progesterone receptor modulator ulipristal acetate (SPRM-UPA)?</p><p><strong>Summary answer: </strong>Application of an unbiased method for analysis of MR images showed that treatment of HMB with SPRM-UPA was not associated with a significant reduction in the volume of the uterus or in the volume of uterine fibroids.</p><p><strong>What is known already: </strong>SPRM-UPA shows therapeutic efficacy for treating HMB. However, the mechanism of action (MoA) is not well understood and there have been mixed reports, using potentially biased methodology, regarding whether SPRM-UPA has an effect on the volume of the uterus and fibroids.</p><p><strong>Study design size duration: </strong>In a prospective clinical study (with no comparator), 19 women with HMB were treated over a period of 12 months with SPRM-UPA and uterine and fibroid size were assessed with high resolution structural MRI and stereology.</p><p><strong>Participants/materials setting methods: </strong>A cohort of 19 women aged 38-52 years (8 with and 11 without fibroids) were treated with three 12-week courses of 5 mg SPRM-UPA given daily, with four weeks off medication in-between treatment courses. Unbiased estimates of the volume of uterus and total volume of fibroids were obtained at baseline, and after 6 and 12 months of treatment, by using the Cavalieri method of modern design-based stereology in combination with magnetic resonance imaging (MRI).</p><p><strong>Main results and the role of chance: </strong>Bland-Altman plots showed good intra-rater repeatability and good inter-rater reproducibility for measurement of the volume of both fibroids and the uterus. For the total patient cohort, two-way ANOVA did not show a significant reduction in the volume of the uterus after two or three treatment courses of SPRM-UPA (<i>P</i> = 0.51), which was also the case when the groups of women with and without fibroids were considered separately (<i>P</i> = 0.63). One-way ANOVA did not show a significant reduction in total fibroid volume in the eight patients with fibroids (<i>P</i> = 0.17).</p><p><strong>Limitations reasons for caution: </strong>The study has been performed in a relatively small cohort of women and simulations that have subsequently been performed using the acquired data have shown that for three time points and a group size of up to 50, with alpha (Type I Error) and beta (Type II Error) set to 95% significance and 80% power, respectively, at least 35 patients would need to be recruited in order for the null hypothesis (that there is no significant reduction in total fibroid volume) to be potentially rejected.</p><p><strong>Wider implications of the findings: </strong>The imaging protocol that we have developed represents a","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 3","pages":"hoad021"},"PeriodicalIF":8.3,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9619544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The lack of evidence behind over-the-counter antioxidant supplements for male fertility patients: a scoping review.","authors":"Wiep R de Ligny, Kathrin Fleischer, Hilde Grens, Didi D M Braat, Jan Peter de Bruin","doi":"10.1093/hropen/hoad020","DOIUrl":"10.1093/hropen/hoad020","url":null,"abstract":"<p><strong>Study question: </strong>What is the evidence for over-the-counter antioxidant supplements for male infertility?</p><p><strong>Summary answer: </strong>Less than half of over-the-counter antioxidant supplements for male fertility patients have been tested in a clinical trial, and the available clinical trials are generally of poor quality.</p><p><strong>What is known already: </strong>The prevalence of male infertility is rising and, with this, the market for supplements claiming to improve male fertility is expanding. Up to now, there is limited data on the evidence for these over-the-counter supplements.</p><p><strong>Study design size duration: </strong>Amazon, Google Shopping and other relevant shopping websites were searched on 24 June 2022 with the following terms: 'supplements', 'antioxidants', 'vitamins', AND 'male fertility', 'male infertility', 'male subfertility', 'fertility men', 'fertility man'. All supplements with a description of ingredients in English, Dutch, French, Spanish, or German were included. Subsequently, Pubmed and Google Scholar were searched for studies that included the supplements.</p><p><strong>Participants/materials setting methods: </strong>Inclusion criteria were supplements with antioxidant properties, of which the main purpose was to improve male fertility. Included supplements must be available without a doctor's prescription. Supplements containing plant extracts were excluded, as well as supplements of which the content or dosage was not clear. The ingredients, dosage, price and health claims of the supplements were recorded. We assessed whether substances in the supplements exceeded the recommended dietary allowance (RDA) or tolerable upper intake level (UL). All clinical trials and animal studies investigating included supplements were selected for this review. Clinical trials were assessed for risk of bias with a risk of bias tool appropriate for the study design.</p><p><strong>Main results and the role of chance: </strong>There were 34 eligible antioxidant supplements found, containing 48 different active substances. The average price per 30 days was 53.10 US dollars. Most of the supplements (27/34, 79%) contained substances in a dosage exceeding the recommended daily allowance (RDA). All manufacturers of the supplements made health claims related to the improvement of sperm quality or male fertility. For 13 of the 34 supplements (38%), published clinical trials were available, and for one supplement, only an animal study was found. The overall quality of the included studies was poor. Only two supplements were tested in a good quality clinical trial.</p><p><strong>Limitations reasons for caution: </strong>As a consequence of searching shopping websites, a comprehensive search strategy could not be formulated. Most supplements were excluded because they contained plant extracts or because supplement information was not available (in an appropriate language).</p><p><strong>Wider implications o","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 3","pages":"hoad020"},"PeriodicalIF":8.3,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9601415","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":"Reply to: 'Hiding in plain sight' and 'Caution is needed when communicating analyses based on an apple to orange comparison'.","authors":"Pedro Melo, Simon Wood, Georgios Petsas, Yealin Chung, Julija Gorodeckaja, Malcolm J Price, Arri Coomarasamy","doi":"10.1093/hropen/hoad017","DOIUrl":"10.1093/hropen/hoad017","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 3","pages":"hoad017"},"PeriodicalIF":0.0,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9576471","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}