Top 10 priorities for future infertility research : an international consensus development study

Acknowledgements: We would like to thank the initial survey, interim prioritization survey, and consensus development meeting participants, and colleagues at the Cochrane Gynaecology and Fertility Group, University of Auckland, New Zealand. Funding This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Foundation, and Maurice and Phyllis Paykel Trust. The funders had no role in the design and conduct of the study, the collection, management, analysis, or interpretation of data, or manuscript preparation. Ben Mol is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). Siladitya Bhattacharya was supported by the Auckland Foundation Seelye Travelling Fellowship. This article has not been externally peer reviewed.yThis article has been published simultaneously in Human ReproductionPeer reviewedPublisher PD

Developing a core outcome set for future infertility research : an international consensus development study

Acknowledgements We would like to thank the Delphi survey and consensus development meeting participants and colleagues at the Cochrane Gynaecology and Fertility Group, University of Auckland, New Zealand. Funding This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. This article has not been externally peer reviewed. This article has been published simultaneously in Fertility and Sterility.Peer reviewedPublisher PD

The Sexual Impact of Infertility Among Women Seeking Fertility Care.

IntroductionInfertility affects approximately 6.7 million women in the United States. Couples with infertility have significantly more anxiety, depression, and stress. This is compounded by the fact that almost 40% of couples undergoing assisted reproduction technology still cannot conceive, which can have an ongoing effect on quality of life, marital adjustment, and sexual impact.AimTo assess the sexual impact of infertility in women undergoing fertility treatment.MethodsThis study is a cross-sectional analysis of women in infertile couples seeking treatment at academic or private infertility clinics. Basic demographic information was collected. Respondents were surveyed regarding sexual impact and perception of their infertility etiology. Multivariate regression analyses were used to identify factors independently associated with increased sexual impact.Main outcome measureSexual impact of perceived fertility diagnosis.ResultsIn total, 809 women met the inclusion criteria, of whom 437 (54%) agreed to participate and 382 completed the sexual impact items. Most of the infertility was female factor only (58.8%), whereas 30.4% of infertility was a combination of male and female factors, 7.3% was male factor only, and 3.5% was unexplained infertility. In bivariate and multivariate analyses, women who perceived they had female factor only infertility reported greater sexual impact compared with woman with male factor infertility (P = .01). Respondents who were younger than 40 years experienced a significantly higher sexual impact than respondents older than 40 years (P < .01). When stratified by primary and secondary infertility, respondents with primary infertility overall reported higher sexual impact scores.ConclusionIn women seeking fertility treatment, younger age and female factor infertility were associated with increased sexual impact and thus these women are potentially at higher risk of sexual dysfunction. Providers should consider the role young age and an infertility diagnosis plays in a women's sexual well-being

Standardizing definitions and reporting guidelines for the infertility core outcome set : an international consensus development study

Acknowledgments: We would like to thank the consensus development meeting participants and colleagues at the Cochrane Gynaecology and Fertility Group, University of Auckland, New Zealand. Funding This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund, and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis, or interpretation of data, or manuscript preparation. Siladitya Bhattacharya was supported by the University of Auckland Foundation Seelye Travelling Fellowship. Ben Mol is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). his article has not been externally peer reviewed.yThis article has been published simultaneously in Human ReproductionPeer reviewedPublisher PD

Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy

BACKGROUND: Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. METHODS: In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. RESULTS: In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5-101.8, versus 104.4, 95% CI: 100.4-108.4, P = 0.001, Q < 0.001 [Q refers to the false discovery rate adjusted P value], and 3.9, 95% CI: 3.6-4.3, versus 4.5, 95% CI: 4.1-4.9, P = 0.005, Q = 0.045, respectively). A significant difference in diastolic blood pressure was found, with higher values in chemotherapy-exposed (61.1, 95% CI: 59.0 to 63.2) versus control children (56.0, 95% CI 54.1 to 57.8) (P < 0.001, Q < 0.001) and in a subgroup of 59 anthracycline-exposed (61.8, 95% CI: 59.3 to 64.4) versus control children (55.9, 95% CI: 53.6 to 58.1) (P < 0.001, Q = 0.02). CONCLUSIONS: Children prenatally exposed to maternal cancer and its treatment are at risk for lower verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, but other cognitive functions and cardiac outcomes were normal at the age of 6 years. CLINICAL TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov, NCT00330447

Demographics of infertility and management of unexplained infertility

Peer reviewedPostprin

Management and outcome of colorectal cancer during pregnancy: report of 41 cases

BACKGROUND: Colorectal cancer in pregnancy is rare, with an incidence of 0.8 per 100,000 pregnancies. Advanced disease (stage III or IV) is diagnosed more frequently in pregnant patients. We aimed to review all cases of colorectal cancer in pregnancy from the International Network on Cancer, Infertility and Pregnancy database in order to learn more about this rare disease and improve its management. METHODS: Data on the demographic features, symptoms, histopathology, diagnostic and therapeutic interventions and outcomes (obstetric, neonatal and maternal) were analysed. RESULTS: Twenty-seven colon and 14 rectal cancer cases were identified. Advanced disease was present in 30 patients (73.2%). During pregnancy, 21 patients (51.2%) received surgery and 12 patients (29.3%) received chemotherapy. Thirty-three patients (80.5%) delivered live babies: 21 by caesarean section and 12 vaginally. Prematurity rate was high (78.8%). Eight babies were small for gestational age (27.6%). Three patients (10.7%) developed recurrence of disease. Overall 2-year survival was 64.4%. CONCLUSION: Despite a more frequent presentation with advanced disease, colorectal cancer has a similar prognosis in pregnancy when compared with the general population. Diagnostic interventions and treatment should not be delayed due to the pregnancy but a balance between maternal and foetal wellbeing must always be kept in mind. ispartof: ACTA CHIRURGICA BELGICA vol:119 issue:3 pages:166-175 ispartof: location:England status: publishe

Evidence-based guideline : unexplained infertility

The GDG would like to acknowledge the help of many clinicians and professional organizations who refereed the content of the guideline and submitted helpful comments to the draft version. Special thanks to the steering committee of the ESHRE SIG Andrology for the feedback on the formulations of the key questions and the final draft of the guideline.Peer reviewe

The piRNA-pathway factor FKBP6 is essential for spermatogenesis but dispensable for control of meiotic LINE-1 expression in humans

Infertility affects around 7% of the male population and can be due to severe spermatogenic failure (SPGF), resulting in no or very few sperm in the ejaculate. We initially identified a homozygous frameshift variant in FKBP6 in a man with extreme oligozoospermia. Subsequently, we screened a total of 2,699 men with SPGF and detected rare bi-allelic loss-of-function variants in FKBP6 in five additional persons. All six individuals had no or extremely few sperm in the ejaculate, which were not suitable for medically assisted reproduction. Evaluation of testicular tissue revealed an arrest at the stage of round spermatids. Lack of FKBP6 expression in the testis was confirmed by RT-qPCR and immunofluorescence staining. In mice, Fkbp6 is essential for spermatogenesis and has been described as being involved in piRNA biogenesis and formation of the synaptonemal complex (SC). We did not detect FKBP6 as part of the SC in normal human spermatocytes, but small RNA sequencing revealed that loss of FKBP6 severely impacted piRNA levels, supporting a role for FKBP6 in piRNA biogenesis in humans. In contrast to findings in piRNA-pathway mouse models, we did not detect an increase in LINE-1 expression in men with pathogenic FKBP6 variants. Based on our findings, FKBP6 reaches a "strong" level of evidence for being associated with male infertility according to the ClinGen criteria, making it directly applicable for clinical diagnostics. This will improve patient care by providing a causal diagnosis and will help to predict chances for successful surgical sperm retrieval

Standardizing definitions and reporting guidelines for the infertility core outcome set : an international consensus development study

Acknowledgments We would like to thank the consensus development meeting participants and colleagues at the Cochrane Gynaecology and Fertility Group, University of Auckland, New Zealand. Funding This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data or manuscript preparation. Siladitya Bhattacharya was supported by the University of Auckland Foundation Seelye Travelling Fellowship. B.W.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548) This article has not been externally peer reviewed. This article has been published simultaneously in Fertility and SterilityPeer reviewedPublisher PD