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Recent national studies on awareness of folic acid (FA) prior to pregnancy among Canadian women are lacking. Using the 2017-2018 Canadian Community Health Survey, we aimed to estimate prevalence and risk factors associated with Canadian women who reported they were unaware of the benefits of FA supplementation before pregnancy. Prevalence of unawareness of FA was 22.1%. Lower education, lack of a health care provider, low household income, and an immigrant background were associated with greater odds of unawareness of the benefits of FA supplementation. Persistent associations with measures of social disadvantage and social determinants of health emphasize the need for new targeted public health campaigns., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Purpose: In vitro fertilization (IVF) is associated with abnormal trophoblast invasion and resultant decreased levels of circulating placental biomarkers such as placental growth factor (PlGF). Our objective was to evaluate maternal serum levels of second/third trimester PlGF, sonographic placental parameters, and clinical outcomes among IVF frozen embryo transfer (FET) pregnancies with and without embryo trophectoderm biopsy., Methods: This was a retrospective study of pregnant patients who conceived using a single frozen embryo transfer (FET) and gave birth between 30 January 2018 and 31 May 2021. We compared PlGF levels, sonographic placental parameters, and clinical outcomes between FET with biopsy and FET without biopsy groups., Results: The median PlGF level was 614.5 pg/mL (IQR 406-1020) for FET pregnancies with biopsy, and 717.0 pg/mL (IQR 552-1215) for FET pregnancies without biopsy. The adjusted mean difference was 190.9 pg/mL lower in the FET biopsy group (95% CI, -410.6, 28.8; p = 0.088). There were no statistically significant differences in placental parameters or clinical pregnancy outcomes., Conclusion: This exploratory study demonstrated a possible trend toward lower maternal serum PlGF in the pregnancies conceived with FET using a biopsied embryo. Further investigation is warranted into the potential placental health effects of trophectoderm biopsy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To explore if a day 7 blastocyst is predictive of the reproductive potential of sibling day 5 or day 6 blastocysts?, Methods: Retrospective cohort of autologous frozen embryo transfers (FET), February 2019 to April 2022. Cycles divided into groups 1 to 5, according to the day of embryo cryopreservation and the presence of a day 7 blastocyst sibling within the cohort: group 1/group 2-day 5 blastocyst without/with a day 7 sibling, group 3/group 4-day 6 blastocyst without/with a day 7 sibling, group 5-day 7 blastocyst. Clinical, ongoing pregnancy and miscarriage rates, cycle, and patient characteristics are reported. Multivariable generalized estimating equations (GEE) logistic regression analysis accounts for confounders and assesses the effect of a sibling day 7 blastocyst on ongoing pregnancy rates of day 5 or day 6 blastocyst FETs., Results: Ongoing pregnancy rates are 38.4%, 59.5%, 30.8%, 32.7%, and 4.4% in groups 1-5, respectively. When correcting for maternal age, number of oocytes retrieved and discarded per cohort, and ploidy, embryos cryopreserved on either day 6 or day 7 have reduced odds of ongoing pregnancy after FET compared to day 5 blastocysts (OR = 0.76, IQR [0.61-0.95], p-value = 0.01). However, the presence of a day 7 sibling does not significantly affect odds of ongoing pregnancy of day 5 or day 6 blastocysts compared to the same-day blastocyst without a day 7 sibling (p-value = 0.20 and 0.46, respectively). This finding is consistent within both the Preimplantation Genetic Testing for Aneuploidy (PGT-A) unscreened and screened (euploid) embryo subgroups., Conclusions: Day of embryo cryopreservation significantly affects ongoing pregnancy rates. However, day 7 embryos within a cohort do not affect the reproductive potential of sibling day 5 and day 6 blastocysts, suggesting that slow embryo development is an embryo-specific trait., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The objective of this study was to gather Ontario clinicians' and public members' views on the design of a pre-conception patient education program., Methods: In this mixed-methods study, online surveys comprised of rank order, multiple choice, and short answer questions were completed by clinicians and public members. Semi-structured focus groups consisting of 2-6 participants each were then held via videoconference. Demographic variables and survey responses were analyzed quantitatively using descriptive and summary statistics. Descriptive thematic qualitative analysis using the constant comparative method of grounded theory was completed on each transcript to generate themes., Results: A total of 168 public members and 43 clinicians in Ontario completed surveys, while 11 clinicians and 11 public members participated in the focus groups. A pre-conception program in Ontario was felt to be important. An individual appointment with a primary care provider was the favoured program format per survey responses, whereas a virtual format with an interactive component was preferred among focus group participants. Important topics to include were pre-conception health (infertility, genetic screening, folic acid), prenatal and postpartum counselling (diet, activity, substance use, prenatal care, postpartum course), and medical optimization in pregnancy (high-risk medical conditions, medications, mental health). Both groups emphasized the need to consider accommodations for marginalized populations and various cultures and languages., Conclusion: A standardized pre-conception patient education program is felt to be of high value by Ontario clinicians and public members. A pre-conception program may help improve obstetrical outcomes and decrease rates of major congenital anomalies in Ontario., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Background: Previous research has demonstrated that patients have difficulty with the decision to undergo non-urgent egg freezing (EF). This study aimed to investigate the decisional difficulties and possible decisional support mechanisms for patients considering EF, and for their providers., Methods: This qualitative study involved a needs assessment via individual interviews. Participants included patients considering EF at one academic fertility clinic and providers from across Canada who counsel patients considering EF. 25 participants were included (13 providers and 12 patients). The interview guide was developed according to the Ottawa Decision Support Framework. Interviews were transcribed, and transcripts analyzed for themes and concepts using NVIVO 12., Findings: Multiple factors contributing to decisional difficulty were identified, including: (1) multiple reproductive options available with differing views from patients/providers regarding their importance; (2) a decision typically made under the pressure of reproductive aging; (3) uncertainty surrounding the technology/inadequate outcome data; (4) the financial burden of EF; (5) inherent uncertainty relating to potential decision regret; and (6) differing perceptions between patients/providers regarding the role providers should play in the decision. Additionally, potential sources of decisional support were identified, including provision of basic information before and/or during initial consultation, followed by an opportunity during or after initial consultation for clarifying information and helping with value judgements. Individualized counselling based on patient values, adequate follow-up, psychosocial counselling, and peer support were also emphasized., Conclusions: More decisional support for women considering EF is needed. Suggestions include a patient decision aid in conjunction with modified healthcare provider counselling, support and follow up., (© 2023. The Author(s).)

Purpose: Endometrial histology on hematoxylin and eosin (H&E)-stained preparations provides information associated with receptivity. However, traditional histological examination by Noyes' dating method is of limited value as it is prone to subjectivity and is not well correlated with fertility status or pregnancy outcome. This study aims to mitigate the weaknesses of Noyes' dating by analyzing endometrial histology through deep learning (DL) algorithm to predict the chance of pregnancy., Methods: Endometrial biopsies were taken during the window of receptivity from healthy volunteers in natural menstrual cycles (group A) and infertile patients undergoing mock artificial cycles (group B). H&E staining was performed followed by whole slide image scanning for DL analysis., Results: In a proof-of-concept trial to differentiate group A (n=24) vs. B (n=37), a DL-based binary classifier was trained, cross-validated, and achieved 100% for accuracy. Patients in group B underwent subsequent frozen-thawed embryo transfers (FETs) and were further categorized into "pregnant (n=15)" or "non-pregnant (n=18)" sub-groups based on the outcomes. In the following trial to predict pregnancy outcome in group B, the DL-based binary classifier yielded 77.8% for accuracy. Its performance was further validated by an accuracy of 75% in a "held-out" test set where patients had euploid embryo transfers. Furthermore, the DL model identified histo-characteristics including stromal edema, glandular secretion, and endometrial vascularity as important features related to pregnancy prediction., Conclusions: DL-based endometrial histology analysis demonstrated its feasibility and robustness in pregnancy prediction for patients undergoing FETs, indicating its value as a prognostic tool in fertility treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The decision to undergo non-urgent egg freezing (EF) is complex for patients and providers supporting them. Though prior studies have explored patient perspectives, no study has also included the separate perspectives of providers., Methods: This qualitative study involved semi-structured individual interviews exploring the decision to undergo EF. Participants included patients considering EF at one academic fertility clinic and providers who counsel patients about EF from across Canada. Data analysis was accomplished using thematic analysis. Data saturation was met after interviewing 13 providers and 12 patients., Findings: Four themes were identified and explored, illuminating ways in which patients and providers navigate decision-making around EF: (1) patients viewed EF as a 'back-up plan' for delaying the decision about whether to have children, while providers were hesitant to present EF in this way given the uncertainty of success; (2) providers viewed ovarian reserve testing as essential while patients believed it unnecessarily complicated the decision; (3) patients and providers cited a need for change in broader societal attitudes regarding EF since social stigma was a significant barrier to decision-making; and (4) commonality and peer support were desired by patients to assist in their decision, although some providers were hesitant to recommend this to patients., Conclusions: In conclusion, the decision to undergo EF is complex and individual patient values play a significant role. In some areas, there is disconnect between providers and patients in their views on how to navigate EF decision-making, and these should be addressed in discussions between providers and patients to improve shared decision-making., (© 2023. The Author(s).)

Research Question: Are the demographics and clinical outcomes similar for patients aged ≥40 but <43 years seeking IVF in Ontario, Canada, before and after implementation of the Ontario Fertility Program (OFP), which supports public funding of IVF up to age 43?, Design: Retrospective database review using the Canadian Assisted Reproductive Technologies Registry Plus (CARTR Plus) and Better Outcomes Registry & Network (BORN) Ontario databases. Cycles from women who underwent autologous IVF and who were aged ≥40 and <43 years were analysed during a 2-year period prior to (2014-2015) and after (2016-2017) introduction of publicly funded IVF through the OFP., Results: There was an almost doubling of treatment cycles in women aged 40-42 in Ontario after the OFP launch. Clinical pregnancy rate per cycle start (17.0% versus 13.3%, P < 0.001) and cumulative clinical pregnancy rate per stimulation cycle (20.5% versus 16.8%, P < 0.001) were statistically higher in women before OFP implementation. While cumulative live birth rate per cycle start was statistically lower after funding was introduced (12.5% versus 10.5%, P = 0.027), the clinical importance of this difference appears small. Outcomes were above the 10% live birth per cycle threshold recommended by the Advisory Process for Infertility Services panel, commissioned by the Ministry of Health, to determine access to publicly funded IVF., Conclusions: Use of IVF in women over age 40 doubled with access to OFP funding; however, eligibility criteria based on age still meet the target of achieving a cumulative live birth rate of at least 10%., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Reproductive decision-making is difficult for BRCA-positive women. Our objective was to assess the complexities of decision-making and identify decisional supports for patients and providers when discussing reproductive options prior to risk-reducing salpingo-oophorectomy (RRSO)., Methods: This study was of qualitive design, using data collection via semi-structured interviews conducted from November 2018 to October 2020. Individuals were included if they were identified to provide care to BRCA-positive women. In total, 19 providers were approached and 15 consented to participate. Providers were recruited from three clinics in Toronto, Ontario located at academic centers: [1] A familial ovarian cancer clinic, [2] A familial breast cancer clinic and [3] A fertility clinic, all of which treat carriers of the BRCA1/BRCA2 genetic mutation. The interview guide was developed according to the Ottawa Decision Support Framework and included questions regarding reproductive options available to patients, factors that impact the decision-making process and the role of decisional support. Interviews were transcribed and transcripts were analyzed thematically using NVIVO 12., Results: Providers identified three major decisions that reproductive-aged women face when a BRCA mutation is discovered: [1] "Do I want children?"; [2] "Do I want to take the chance of passing on this the mutation?"; and [3] "Do I want to carry a child?" Inherent decision challenges that are faced by both providers and patients included difficult decision type, competing options, scientifically uncertain outcomes, and challenging decision timing. Modifiable decisional needs included: inadequate knowledge, unrealistic expectations, unclear values and inadequate support or resources. Identified clinical gaps included counselling time constraints, lack of reliable sources of background information for patients or providers and need for time-sensitive, geographically accessible, and centralized care., Conclusion: Our study identified a need for a patient information resource that can be immediately provided to patients who carry a BRCA genetic mutation. Other suggestions for clinical practice include more time during consultation appointments, adequate follow-up, value-centric counseling, access to psychosocial support, and a specialized decisional coach., (© 2022. The Author(s).)

The assessment of anti-mullerian hormone (AMH) pre- and post-gonadotoxic treatment helps define reproductive potential in young female adults facing cancer treatment. Normative childhood AMH levels are not well defined. Our objective was to help establish accurate pediatric reference intervals (RIs) for which AMH can be used to assess AMH in pediatric/adolescent survivors. Healthy female volunteers aged 6-<19 years were recruited from the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort. 300 serum samples were analyzed for AMH using an automated assay. Basic demographics and menstrual cycle data on the subjects were recorded at time of sample collection. Serum AMH distribution and RIs (2.5th and 97.5th percentiles) were established in four age groups. One recommended RI (0.98-7.84 ng/mL) was established for females aged 6-<19 years after outlier removal. Females 6-<9 years demonstrated significantly lower mean AMH concentration than did females 9-<12 years (Mean ± SD: 3.18 ± 1.62 and 4.16 ± 2.55 ng/mL, respectively), who in turn demonstrated significantly higher AMH concentrations than those aged 12-<15 years (Mean ± SD: 3.75 ± 1.61 ng/mL). Statistical differences are unlikely to be clinically meaningful. Menstrual status and ethnicity did not significantly impact AMH concentrations (p = 0.787 and p = 0.0965, respectively). This is the largest series of its kind using a contemporary, automated, single-batched AMH assay in a healthy pediatric female cohort. In conjunction with future data points and longitudinal data, the RI established may be a useful adjunct to reproductive health counselling delivered to pediatric cancer patients requiring fertility damaging therapies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Endometrial laminin subunit beta-3 (LAMB3) is a candidate gene whose expression distinguishes the endometrial window of receptivity (WOR) in human. This study aims to examine endometrial LAMB3 levels in patients with repeated implantation failure (RIF), in order to assess the ability of LAMB3 to predict pregnancy outcome., Methods: Endometrial biopsies were taken during the WOR from 21 healthy volunteers in natural menstrual cycles and from 50 RIF patients in mock cycles prior to frozen embryo transfer (FET) cycles. Immunohistochemistry (IHC) staining of LAMB3 was performed, and the H-score was correlated with the pregnancy outcome in subsequent FETs., Results: In healthy volunteers, endometrial LAMB3 was demonstrated to be highly expressed during the WOR with the staining exclusively in the cytoplasm of the epithelial cells. In a discovery set of RIF patients, the LAMB3 expression level was found to be significantly higher in those who conceived compared to those who did not in subsequent FETs. A receiving operator characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.7818 (95% confidence interval 59.92-96.44%) with an H-score cutoff of 4.129 to differentiate cases with positive or negative pregnancy outcomes. This cutoff achieved an accuracy of 75% in pregnancy prediction in a following validation set of RIF patients, in which the pregnancy rate in subsequent FETs was three-fold higher when the mock cycle LAMB3 H-score was ≥ 4.129 compared to < 4.129., Conclusions: IHC measurement of endometrial LAMB3 expression could be a promising prognostic method to predict pregnancy outcome for RIF patients undergoing FETs., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To optimize a method of isolating extracellular vesicles (EVs) from uterine fluid and to characterize small non-coding RNAs (sncRNAs) from the EVs, with the goal of identifying novel receptivity-associated biomarkers., Design: Longitudinal study comparing sncRNA expression profiles from endometrial EVs., Setting: University-affiliated, hospital-based fertility clinic., Patient(s): Healthy volunteers with no history of infertility (Group A) and women receiving controlled ovarian stimulation (COS)-in vitro fertilization treatment (Group B)., Interventions(s): In Group A, EVs were isolated from uterine fluid obtained on luteinizing hormone (LH)+2 and LH+7 in one natural menstrual cycle. In Group B, EVs were isolated from uterine fluid obtained on human chorionic gonadotropin (hCG)+2 and hCG+7 in one COS cycle. RNAs extracted from EVs were profiled using next-generation sequencing., Main Outcome Measure(s): Differential EV-sncRNAs between LH+2 and LH+7 (Group A), between hCG+2 and hCG+7 (Group B), and between pregnant and nonpregnant in vitro fertilization cycles (Group B)., Result(s): Ultracentrifugation was validated as the most efficient method to isolate EVs from uterine fluid. We identified 12 endometrial EV-sncRNAs (11 microRNAs and 1 piwi-interacting RNA) as receptivity-associated transcripts conserved in both natural and COS cycles. These sncRNAs were associated strongly with biological functions related to immune response, extracellular matrix, and cell junction. Within COS cycles, we also identified a group of EV-sncRNAs that exhibited differential expression in patients who conceived versus those who did not, with hsa-miR-362-3p most robustly overexpressed in the nonpregnant patients., Conclusion(s): This study is the first to profile comprehensively sncRNAs in endometrial EVs from uterine fluid and identify sncRNA biomarkers of endometrial receptivity and implantation success., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

For patients with recurrent implantation failure in IVF, histologic or transcriptomic testing of the endometrium during the mid-secretory phase is often considered. Histological dating of endometrial biopsies (Noyes criteria) can determine if endometrial morphology is consistent with the period of receptivity. Alternatively, endometrial tissue can be sent for a commercial Endometrial Receptivity Array (ERA) test which characterizes the gene expression of the endometrium using a panel of 238 genes that have been implicated in endometrial receptivity. This study aimed to compare the two tests to assess their concordance and to examine the ability of the ERA to successfully predict implantation and pregnancy in a subsequent personalized embryo transfer. A retrospective review was done of 97 patients with a history of implantation failure who underwent an ERA, 35 of whom had histologic dating on the same sample. ERA and histology were classified as 'concordant' when samples were receptive by both tests or non-receptive by both tests. The ERA result was then used to personalize the embryo transfer day, and pregnancy rates from the first subsequent frozen transfer cycle were analyzed. The results indicated that there is poor concordance between ERA and histological dating with only 40.0% agreement and a kappa (95%CI) = -0.18 (-0.50, 0.14). According to the ERA, 48.5% of biopsies were receptive, 47.4% were non-receptive and 2.01% were insufficient tissue for analysis. The clinical pregnancy rate in patients shown to be receptive by ERA was 26.7% and non-receptive was 22.5% following the subsequent personalized ET (p = 0.66). This study concludes that there is a high degree of discordance between histological dating of the endometrium and molecular analysis by ERA. There was no evidence of clinical benefit when embryo transfer was personalized according to ERA in patients with a history of implantation failure.

Study Question: Can the priorities for future research in infertility be identified?, Summary Answer: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified., What Is Known Already: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems., Study Design, Size, Duration: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care., Participants/materials, Setting, Methods: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance., Main Results and the Role of Chance: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science., Limitations, Reasons for Caution: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions., Wider Implications of the Findings: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda., Study Funding/competing Interest(s): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand and Maurice and Phyllis Paykel Trust. G.D.A. reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. A.W.H. reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research and Wellbeing of Women and consultancy fees from AbbVie, Ferring, Nordic Pharma and Roche Diagnostics. M.L.H. reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. N.P.J. reports research sponsorship from AbbVie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics and Vifor Pharma. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from AbbVie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. E.H.Y.N. reports research sponsorship from Merck. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring and retains a financial interest in NexHand. J.S. reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring and being a clinical subeditor of Human Fertility. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form., Trial Registration Number: N/A., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: This study sought to answer the following question: What are the complications and assisted reproductive technology outcomes among women with hydrosalpinges managed by hysteroscopic microinsert tubal occlusion compared with women with hydrosalpinges managed by laparoscopic proximal tubal occlusion or salpingectomy?, Methods: This was a retrospective cohort study conducted from January 2009 to December 2014 at two academic, tertiary care, in vitro fertilization centres in Toronto, Ontario. All patients (n = 52) who underwent hysteroscopic tubal occlusion for hydrosalpinges were identified. Patients who proceeded with embryo transfer cycles after hysteroscopic microinsert (n = 33) were further age matched to a cohort of patients who underwent embryo transfer after laparoscopic proximal tubal occlusion or salpingectomy (n = 33). Main outcome measures were clinical pregnancy rate per patient and per embryo transfer cycle., Results: Among 33 patients, there were 39 fresh and 37 frozen embryo transfer cycles in the hysteroscopic group (group A); among 33 patients in the laparoscopic group (group B), there were 42 fresh and 29 frozen embryo transfer cycles. The cumulative clinical pregnancy rate in group A and group B was similar (66.7% vs. 69.7%, respectively; P = 0.8). The clinical pregnancy rate per embryo transfer cycle was also similar in both groups (28.9% in group A vs. 32.4% in group B; P = 0.6). There were two incidents of ectopic pregnancy in the laparoscopic group and no ectopic pregnancy in the hysteroscopic group. There were three major complications: tubo-ovarian abscess, distal migration of the coil after microinsert placement, and an acute abdomen following the hysteroscopic procedure., Conclusion: Pregnancy outcomes after hysteroscopic placement of a microinsert for hydrosalpinx management before embryo transfer were comparable to those following laparoscopic proximal tubal occlusion or salpingectomy. However, caution is advised regarding microinsert placement for hydrosalpinges before proceeding with assisted reproductive technology., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to examine a 1-year pilot program aimed at increasing access to fertility preservation (FP) information and services for reproductive-age women newly diagnosed with cancer at a centre geographically remote from a tertiary fertility clinic. An oncofertility nurse navigator (ONN) position was created within the regional cancer centre with the goals of (1) improving local physician knowledge of FP and FP services and (2) improving patient access to FP counselling and services. The ONN identified all women diagnosed with cancer requiring treatment that could impact their fertility and discussed FP options with them and their physicians. As part of a comprehensive program aimed at facilitating access to FP services, the ONN arranged consultations with fertility specialists via telemedicine and coordinated satellite cycle monitoring with a local gynaecologist in order to minimize travel. Patients were surveyed about their reproductive plans, decision-making around FP and experiences with the program. Physicians were surveyed about their engagement with FP services, barriers to FP access and satisfaction with the program. Twenty-two women were eligible for FP during the year-long pilot program. All participated in the study. The most common diagnoses were breast and cervical cancer. At the time of diagnosis, 36.4% of women had no biological children and 68.2% did not desire (more) children. Four women had an FP consultation, and two proceeded with oocyte or embryo cryopreservation. At the end of the pilot program, more physician respondents often or always discussed FP with their patients, stated they frequently refer for FP consultations and stated their patients could obtain FP services in a timely fashion. An ONN within a cancer centre remote from tertiary fertility care can enable access to FP services with minimal need for travel by using local gynaecologic expertise and telemedicine.

Purpose: Oncofertility focuses on providing fertility and endocrine-sparing options to patients who undergo life-preserving but gonadotoxic cancer treatment. The resources needed to meet patient demand often are fragmented along disciplinary lines. We quantify assets and gaps in oncofertility care on a global scale., Methods: Survey-based questionnaires were provided to 191 members of the Oncofertility Consortium Global Partners Network, a National Institutes of Health-funded organization. Responses were analyzed to measure trends and regional subtleties about patient oncofertility experiences and to analyze barriers to care at sites that provide oncofertility services., Results: Sixty-three responses were received (response rate, 25%), and 40 were analyzed from oncofertility centers in 28 countries. Thirty of 40 survey results (75%) showed that formal referral processes and psychological care are provided to patients at the majority of sites. Fourteen of 23 respondents (61%) stated that some fertility preservation services are not offered because of cultural and legal barriers. The growth of oncofertility and its capacity to improve the lives of cancer survivors around the globe relies on concentrated efforts to increase awareness, promote collaboration, share best practices, and advocate for research funding., Conclusion: This survey reveals global and regional successes and challenges and provides insight into what is needed to advance the field and make the discussion of fertility preservation and endocrine health a standard component of the cancer treatment plan. As the field of oncofertility continues to develop around the globe, regular assessment of both international and regional barriers to quality care must continue to guide process improvements., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc. Alexandra S. RashediEmployment: Cigna (I) Stock or Other Ownership: Cigna (I)Antoinette AnazodoResearch Funding: Merck SeronoCassio SartorioEmployment: Vida Centro de Fertilidade Leadership: Vida Centro de Fertilidade Stock or Other Ownership: Vida Centro de FertilidadeCatharina C.M. BeerendonkTravel, Accommodations, Expenses: GoodlifeEllen M. GreenblattConsulting or Advisory Role: Ferring Pharmaceuticals, EMD Serono Travel, Accommodations, Expenses: EMD SeronoFernando M. ReisHonoraria: Politec Saúde (I) Consulting or Advisory Role: Politec Saúde (I) Speakers’ Bureau: UCB (I) Travel, Accommodations, Expenses: Abbott Laboratories (I)Johan SmitzSpeakers’ Bureau: Ferring Pharmaceuticals Travel, Accommodations, Expenses: Ferring PharmaceuticalsMaria T. BourlonLeadership: Medivation, Astellas Pharma Honoraria: Medivation, Astellas Pharma Speakers’ Bureau: Asofarma Research Funding: Bristol-Myers Squibb Travel, Accommodations, Expenses: Janssen PharmaceuticalsMichel De VosHonoraria: Cook Medical Research Funding: Cook MedicalRichard A. AndersonConsulting or Advisory Role: Roche, HRA Pharma, NeRe Pharmaceuticals Speakers’ Bureau: Roche, Beckman Coulter, IBSA Institut Biochimque Research Funding: Ferring Pharmaceuticals Travel, Accommodations, Expenses: IBSA Institut BiochimqueRoberto de A. AntunesConsulting or Advisory Role: Merck Serono Speakers’ Bureau: Merck Serono Travel, Accommodations, Expenses: Merck Serono, MSDTeresa Almeida-SantosConsulting or Advisory Role: Merck, MSD Research Funding: MerckTeresa K. WoodruffResearch Funding: Ferring Pharmaceuticals (Inst) No other potential conflicts of interest were reported., (© 2020 by American Society of Clinical Oncology.)

Purpose: In the accompanying article, "Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe," we showed that specific fertility preservation services may not be offered at various sites around the world because of cultural and legal barriers. We assessed global and regional experiences as well as the legal status of third-party reproduction and adoption to serve as a comprehensive international data set and resource for groups that wish to begin oncofertility interventions., Methods: We provide data on the legalities of third-party assisted reproductive technologies and other family-building options in the 28 oncofertility-practicing countries surveyed., Results: We found regional and country differences that will be important in the development of tailored resources for physicians and for patient brochures that are sensitive to these local restrictions and cultural norms., Conclusion: Because many patients first consult Web-based materials, the formal assessment of the availability of these options provides members of the global oncofertility community with data to which they might otherwise not have ready access to better serve their patients., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Alexandra S. RashediEmployment: Cigna (I) Stock or Other Ownership: Cigna (I)Antoinette AnazodoResearch Funding: Merck SeronoCassio SartorioEmployment: Vida Centro de Fertilidade Leadership: Vida Centro de Fertilidade Stock or Other Ownership: Vida Centro de FertilidadeCatharina C.M. BeerendonkTravel, Accommodations, Expenses: GoodlifeEllen M. GreenblattConsulting or Advisory Role: Ferring Pharmaceuticals, EMD Serono Travel, Accommodations, Expenses: EMD SeronoFernando M. ReisHonoraria: Politec Saúde (I) Consulting or Advisory Role: Politec Saúde (I) Speakers’ Bureau: UCB (I) Travel, Accommodations, Expenses: Abbott Laboratories (I)Flor SánchezPatents, Royalties, Other Intellectual Property: patent pendingJohan SmitzSpeakers’ Bureau: Ferring Pharmaceuticals Travel, Accommodations, Expenses: Ferring PharmaceuticalsMaria T. BourlonLeadership: Medivation, Astellas Pharma Honoraria: Medivation, Astellas PharmaRichard A. AndersonConsulting or Advisory Role: Roche, HRA Pharma, NeRe Pharmaceuticals Speakers’ Bureau: Roche, Beckman Coulter, IBSA Institut Biochimque Research Funding: Ferring Pharmaceuticals Travel, Accommodations, Expenses: IBSA Institut BiochimqueRoberto de A. AntunesConsulting or Advisory Role: Merck Serono Travel, Accommodations, Expenses: Merck Serono, MSDSergio RomeroPatents, Royalties, Other Intellectual Property: patent pendingTeresa Almeida-SantosConsulting or Advisory Role: Merck, MSD Research Funding: Merck SeronoTeresa K. WoodruffResearch Funding: Ferring Pharmaceuticals (Inst) No other potential conflicts of interest were reported., (© 2020 by American Society of Clinical Oncology.)

Germline BRCA1 or BRCA2 mutations (mtBRCA1 and mtBRCA2) increase risk for high-grade serous ovarian cancer (HGSOC), the most commonly diagnosed epithelial ovarian cancer histotype. Other identified risk factors for this cancer, which originates primarily in the distal fallopian tube epithelium (FTE), implicate ovulation, during which the FTE cells become transiently exposed to follicular fluid (FF). To test whether mtBRCA1 or mtBRCA2 nonmalignant FTE cells respond differently to periovulatory FF exposure than control patient FTE cells, gene expression profiles from primary FTE cultures derived from BRCA1 or BRCA2 mutation carriers or control patients were compared at baseline, 24 hours after FF exposure, and 24 hours after FF replacement with culture medium. Hierarchical clustering revealed both FF exposure and BRCA mutation status affect gene expression, with BRCA1 mutation having the greatest impact. Gene set enrichment analysis revealed increased NFκB and EGFR signaling at baseline in mtBRCA1 samples, with increased interferon target gene expression, including members of the ISGylation pathway, observed after recovery from FF exposure. Gene set enrichment analysis did not identify altered pathway signaling in mtBRCA2 samples. An inverse relationship between EGFR signaling and ISGylation with BRCA1 protein levels was verified in an immortalized FTE cell line, OE-E6/E7, stably transfected with BRCA1 cDNA. Suppression of ISG15 and ISGylated protein levels by increased BRCA1 expression was found to be mediated by decreased NFκB signaling. These studies indicate that increased NFκB signaling associated with decreased BRCA1 expression results in increased ISG15 and protein ISGylation following FF exposure, which may be involved in predisposition to HGSOC., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aims of this study were to examine the prevalence of Celiac disease (CD) in Canadian women with unexplained infertility versus women with an identifiable cause of infertility and to assess the sensitivity of the point-of-care Biocard Celiac Test Kit versus standard serum serologic testing., Methods: In this prospective cohort study, women aged 18 to 44 who were evaluated for infertility between February 2010 and May 2012 at a tertiary academic care fertility clinic in Toronto, ON, were invited to participate. They were categorized as having unexplained infertility (Cases) or infertility secondary to a known cause (Controls). Women on a gluten-free diet or previously diagnosed with CD were excluded. Outcome measures were the Celiac Questionnaire, serum testing for tissue transglutaminase IgA antibody (anti-tTG IgA), serum IgA levels, and Biocard Celiac Test Kit., Results: Of 685 women approached, 1.2% (4/326) with unexplained infertility and 1.1% (4/359) with an identifiable infertility cause were newly found to have CD. Biocard testing revealed the same results as standard serologic IgA and anti-tTG IgA testing., Conclusion: CD was not more common in women with unexplained infertility than those with an identifiable cause of infertility. These results do not support the routine screening of Canadian women with infertility for CD., (Copyright © 2018. Published by Elsevier Inc.)

The objective of this study was to assess the effects of elevated luteal-phase progesterone levels (PE) and high progesterone/estradiol ratio ('P/E2' ratio) on IVF outcomes, exclusively in GnRH-antagonist cycles with day-5 embryo transfer. PE was not found to have a significant effect on implantation or clinical pregnancy rate (CPR) (OR 0.56, 95% CI 0.25-1.25, p = .16). Elevated 'P/E2' ratio (≥0.55) on trigger day was associated with a poorer response to stimulation and lower clinical pregnancy rates (OR 0.58, 95% CI 0.34-1.00, p = .05). Patients with PE and low 'P/E2' ratio yielded significantly more oocytes than patients with PE and high 'P/E2' ratio. The mean implantation rate per patient decreased by 60% in the group with PE and high 'P/E2' ratio in comparison to the group with PE and low 'P/E2' ratio (17.9%±36.6 vs. 45.5%±47.2, p = .06), although no statistical significance was observed. The detrimental effect of PE may be mitigated by culturing embryos to day-5 before embryo transfer. Combined assessment of serum progesterone and 'P/E2' ratio may predict pregnancy outcome better than progesterone levels alone.

Background: As cure rates for breast cancer improve, there is increasing evidence that late effects of treatment-and impaired fertility in particular-are emerging as important concerns among young breast cancer survivors. Older reports have evaluated the occurrence of amenorrhea after treatment, but few data have been reported about the incidence of biochemical evidence for impaired ovarian function in patients who do not become overtly menopausal., Methods: We conducted a cross-sectional study evaluating anti-Müllerian hormone (amh) in premenopausal chemotherapy-treated breast cancer survivors and control patients. Random serum levels of amh and other relevant clinical data were collected for 100 premenopausal chemotherapy-treated breast cancer survivors and 76 control subjects. Subgroup analyses were performed for women with regular menstrual cycles at the time of amh testing., Results: After adjustment for age, amh was significantly lower in the overall group of patients receiving chemotherapy ( p = 0.002) and in the subgroup reporting normal cycles ( p = 0.03). Cyclophosphamide produced a significant dose-dependent reduction in amh ( p < 0.001); trastuzumab was associated with increased amh in survivors with normal cycles. Overall, serum amh in survivors was roughly equivalent to that measured in control patients 12 years older., Conclusions: Young breast cancer survivors often experience significant impairment of ovarian function despite having normal menstrual cycles after treatment. Those results have important implications for patient counselling and the timing of possible referral to a fertility specialist.

This study assessed whether an obesity-related health status instrument (Edmonton obesity scoring system - EOSS) or body mass index (BMI) better predicted pregnancy rates in overweight women undergoing fertility treatments. A prospective cohort study was conducted on patients with a BMI ≥ 25 kg m(-2) undergoing a fertility treatment cycle (ovulation induction, superovulation, or in vitro fertilization). Obesity-related health status including blood pressure, blood work, health history, and functional assessment were assessed. A total of 101 patients were included in the study with an average age of 36.3 ± 4.2 years and a mean BMI of 31.8 ± 5.2 kg m(-2) . EOSS was found to be statistically predictive of pregnancy rate/cycle (OR 0.51, 95% CI 0.27-0.94; P = 0.03), whereas BMI was not (OR 0.95, 95% CI 0.86-1.05). A similar trend was seen for clinical pregnancy rate/cycle started. However, the association between clinical pregnancy rates and EOSS or BMI did not reach statistical significance (OR 0.53, P = 0.06 and OR 0.98, P = 0.62 respectively). Our results demonstrated that EOSS better predicted pregnancy rates after fertility treatments than BMI. In fact, for every EOSS stage increased by one unit, the odds of pregnancy were approximately halved. A multi-centre study powered for live birth is warranted to establish effective pre-fertility management of overweight women., (© 2016 World Obesity.)

Evidence indicates that high-grade serous ovarian carcinoma (HGSOC) may originate from lesions within the distal fallopian tube epithelium (FTE). Our previous studies indicate that fallopian tube epithelial cells from carriers of germline mutations in breast cancer susceptibility genes exhibit a pro-inflammatory gene expression signature during the luteal phase, suggesting that delayed resolution of postovulatory inflammatory signaling may contribute to predisposition to this ovarian cancer histotype. To determine whether exposure of tubal epithelial cells to periovulatory follicular fluid alters expression of inflammation-associated genes, we used an ex vivo culture system of bovine oviductal epithelial cells. Oviductal cells grown on collagen IV-coated transwell membranes assumed a cobblestone appearance and immunocytochemistry for FoxJ1 and Pax8 indicated that both ciliated and secretory epithelial cells were maintained in the cultures. Oviductal cells were exposed to human follicular fluid or culture medium for 24 h following which total cellular RNA was extracted at various time points. Expression of genes associated with inflammation was determined by quantitative real-time RT-PCR. Exposure to follicular fluid transiently increased the transcript levels of interleukin 8 (IL8) and cyclooxygenase 2 (PTGS2), and decreased the expression of mitochondrial superoxide dismutase (SOD2), glutathione peroxidase 3 (GPX3), disabled homolog 2 (DAB2), and glucocorticoid receptor (NR3C1). Tumor necrosis factor (TNF) and IL6 levels were also decreased while those of nicotinomide phosphoribosyltransferase (NAMPT) were unaffected. This study demonstrates that periovulatory follicular fluid can act directly upon oviductal epithelial cells to alter gene expression that might contribute to early carcinogenic events. Furthermore, these findings illustrate the potential use of bovine oviductal cells to study signaling events implicated in ovarian carcinogenesis.

Objective: To determine whether a minimally invasive approach to sampling endometrial cells that can be applied during an active conception cycle can generate robust biomarker candidates for endometrial receptivity by genomewide gene expression profiling., Design: Longitudinal study comparing gene expression profiles of cells isolated from uterine aspirates collected during the prereceptive and receptive phases of a natural cycle., Setting: University-affiliated hospital., Patient(s): Healthy volunteers, ≤40 years of age, with regular menstrual cycles and no history of infertility., Intervention(s): One menstrual cycle monitored with urinary kits to identify the luteinizing hormone (LH) surge; uterine aspirations collected at LH + 2 days (LH + 2) and at LH + 7; endometrial biopsy obtained on LH + 7; RNA extraction from the cellular material for gene expression profiling, and differential gene expression validated by NanoString assay and cross-validated against a publically available data set., Main Outcome Measure(s): Differentially expressed genes between LH + 2 and LH + 7 samples., Result(s): NanoString assay validated 96% of the 245 genes found differentially expressed at LH + 7. Unsupervised hierarchical clustering of aspiration and biopsy samples demonstrated the concordance of the sampling methods. A predictor gene cassette derived by a shrunken centroid class prediction technique correctly classified the receptive phase within an external data set., Conclusion(s): Uterine aspiration, which can be performed during an active conception cycle, identified robust candidate biomarkers of endometrial receptivity, and will enable their validation by direct correlation with clinical outcomes., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This study explores the attitudes, knowledge, and referring behaviors in fertility preservation among Ontario physicians providing adult cancer care. Ontario physicians with specialties in medical oncology, radiation oncology, gynaecologic oncology, and urology were invited to complete a 48-item questionnaire. A total of 152 questionnaires were available for analysis with a response rate of 23.7%. Seventy-four percent of the physicians indicated that they rarely or never modified cancer treatment due to concern about future fertility. Differences were found in fertility preservation knowledge among respondents in different medical specialties (p < 0.01) and clinical settings (p < 0.05). The frequency of initiating a referral was strongly associated with knowing where to refer patients (p < 0.001). The odds of knowing where to refer cancer patients was higher for physicians who work in a teaching hospital (p < 0.01) and a cancer centre (p < 0.01) compared with those who primarily work in a community setting. About 45% did not know where to refer female patients, and 69.7% rarely ever made a fertility preservation consultation referral for their female patients. The majority of respondents had positive attitudes despite their lack of current knowledge in cryopreservation services and fertility preservation options through assisted reproductive technologies. Our findings provide further insights of the relevance of considering physicians' medical backgrounds and practice settings when designing training modules to raise their awareness in fertility preservation issues.

Objective: To determine the status of oocyte cryopreservation in Canadian assisted reproductive technology (ART) clinics., Methods: An online survey was sent to the medical directors of all Canadian ART clinics between December 2010 and February 2011. The survey included questions about the availability of, the indications for, and the elements of consent for oocyte cryopreservation. Clinics were also asked whether they offered social egg freezing., Results: Twenty of the 28 Canadian ART clinics (71.4%) participated in this survey, and 16 (80%) of those clinics offered oocyte cryopreservation. Forty-five percent of the clinics offered elective oocyte cryopreservation (social egg freezing) for healthy women seeking to prolong fertility. Although most clinics counselled patients that oocyte cryopreservation is experimental, most clinics (87.5%) did not perform the procedure under a protocol approved by a research ethics board. The majority of clinics included most of the essential elements of informed consent during their counselling process. Most clinics that offered social egg freezing performed the procedure for women up to the age of 42, although some clinics did not offer the procedure for women under the age of 35 (28.6%) or over the age of 38 (42.9%)., Conclusion: More than one half of Canadian ART clinics are offering oocyte cryopreservation, although not all clinics offer social egg freezing for healthy women to prolong fertility. Most clinics described the technique as experimental, and the majority included most of the elements of informed consent in their counselling process.

We examined whether estradiol and norethindrone hormone therapy (HT) prevented decline in delayed verbal recall in older women with normal to mildly impaired memory functioning. This was a 2-year, randomized, double-blind, placebo-controlled trial of 142 women aged 61-87, randomly assigned to receive 1 mg 17-beta estradiol daily and 0.35 mg norethindrone 3 days/week or daily placebo for 2 years. The primary outcome was short-delay verbal recall of the California Verbal Learning Test (CVLT). To look for differences in response to HT by baseline short-delay recall, we examined the primary outcome in participants grouped according to whether their baseline scores were below average for the age group or greater than or equal to this score and according to whether they met criteria for Mild Cognitive Impairment (MCI) or not. 133 women completed 1 year of the trial and 128 completed 2 years. Prespecified covariates in all repeated measures analyses of covariance (RANCOVA) included age, education, APOE epsilon4, and prior HT use. RANCOVA showed no overall significant treatment effects at year 1 or year 2. After testing for an interaction, which was significant (p=0.02), we found that women in the HT group who scored at or above the average showed significantly less decline than the placebo group in short-delay verbal recall after 1 year, p=0.007 and 2 years, p=0.01. No treatment effects were found in women below the average in either year. When grouped according to whether the participant met criteria for MCI, the interaction between treatment group and MCI subgroup was not significant. These results suggest that benefits of estrogen exposure may be limited to those with average to above average scores on the delayed verbal recall. HT dose and formulation may have contributed to these beneficial outcomes. Replication is warranted before recommendations can be made in the clinical setting.

Objective: To evaluate the day 3 FSH/LH ratio as a predictor of prognosis in IVF cycles., Design: A retrospective cohort study., Setting: An academic hospital-based fertility center., Patient(s): Two hundred ninety-seven women younger than 40 years old with day 3 FSH levels or=2)., Main Outcome Measure(s): Pregnancy and cancellation rates., Result(s): One-third of patients had a day 3 FSH/LH ratio >or=2.0. Patients with an elevated FSH/LH ratio were more likely to have been placed on an aggressive protocol and had higher starting (257 vs. 232 IU) and total (2484 vs. 2136 IU) FSH doses. Patients with an elevated FSH/LH ratio were more likely to have their cycles cancelled before retrieval (19.6% vs. 8.5%). Although there was a trend toward lower pregnancy rates (24.7% vs. 33.5%), this result was not statistically significant. No clinical pregnancies occurred in 16 women with an FSH/LH ratio >or=3.5., Conclusion(s): An increased FSH/LH ratio of >or=2.0 was associated with poorer IVF cycle outcomes and higher rates of cycle cancellation.

Background: Current legislation in Canada allows for only altruistic gamete donation. Limited clinical data are available on the emotional and psychological impact of altruistic oocyte donation on known donors., Methods: Seventeen women who had donated oocytes to known parties without financial compensation agreed to receive the oocyte donation questionnaire (ODQ) to explore the psychological domains of altruistic oocyte donation., Results: Thirteen ODQ were returned, giving a response rate of 76%. All subjects indicated that they were primarily motivated by a 'desire to give and help' the recipient couple. Most subjects did not find the donation decision difficult but some found the post-donation psychological adjustments challenging. Subjects also indicated that mandatory counselling on the psychological implications of oocyte donation was an important component of cycle preparation. The majority of subjects had disclosed the donation to others and felt that disclosure to the presumptive child was essential., Conclusions: The findings provide clinical materials for conceptualizing the dynamics entailed by known altruistic oocyte donation, with regards to motivation, relationship implications, donor satisfaction and plans for disclosure. The data support the provision of psycho-social support services to help donors dealing with any residual emotional difficulties regardless of the outcome of oocyte donation.

Gestational trophoblastic neoplasia (GTN) is primarily a disease of women of reproductive age. In most instances, it is cured by surgical evacuation of the uterus, with persistent disease being very sensitive to chemotherapy. Hysterectomy, recommended for persistent chemotherapy-resistant uterine disease, may be unacceptable to the woman who wishes to maintain her fertility. Uterine resection of localized disease, with uterine reconstruction, may be a viable alternative. A case is presented of a woman with persistent uterine GTN, treated with localized uterine resection and reconstruction, followed by two successful pregnancies and deliveries. The literature is reviewed and potential pregnancy complications of this management, particularly uterine rupture, are discussed.

Objective: Comparison of two transfer catheters in an IVF program., Design: Prospective, randomized clinical study., Setting: A private tertiary care center for ART., Patient(s): 66 patients < 38 years of age undergoing IVF and/or ICSI., Intervention(s): Patients were randomly assigned to undergo ET using the Tomcat catheter (n = 32) or the TDT catheter (n = 34)., Main Outcome Measure(s): Primary outcome measures were implantation and pregnancy rates. Secondary outcome measures were contamination with blood and/or mucus on the tip of the catheter, cramping or patient discomfort, and time required to complete ET., Result(s): Use of the Tomcat catheter resulted in significantly higher implantation (25.2% vs. 8.4%) and clinical pregnancy rates (47% vs. 14.7%) compared with the TDT catheter. All secondary outcome measures were similar for both catheters., Conclusion(s): The choice of ET catheter may affect the success of IVF-ET cycles. Use of the Tomcat catheter compared with the TDT catheter seems to result in significantly better efficiency of the ET procedure and is more cost effective.

There are numerous reports of successful pregnancy following liver transplantation. Little information is available regarding the incidence and management of infertility in transplant recipients, particularly the use of artificial reproductive technologies. We present a case of a successful twin pregnancy resulting from in-vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI) in a liver transplant recipient, whose partner was a renal transplant recipient with severe oligozoospermia. With careful evaluation and monitoring, and the involvement of appropriate consultants, artificial reproductive technologies can be safely used in transplant recipient couples experiencing infertility.

Polycystic ovarian syndrome (PCOS) is a common disorder associated with hyperandrogenemia and infertility. Abdominal obesity, insulin resistance, and dyslipoproteinemias are other common metabolic disorders typically found in women with PCOS. The cause-effect relationship between hyperandrogenemia and insulin resistance-dyslipoproteinemia remains unclear. In this study, we have investigated the changes in androgenemia, insulin sensitivity, and plasma lipid-lipoprotein levels after laparoscopic ovarian cautery (LOC) for ovulation induction in eight infertile women with clomiphene citrate-resistant PCOS. After LOC, significant decreases in androstenedione (43%), testosterone (48%), and free testosterone (48%) concentrations were observed (P < 0.05). Glucose utilization during an euglycemic-hyperinsulinemic clamp did not change after LOC. In addition, no significant changes after the surgical procedure were observed for cholesterol, triglycerides, and apolipoprotein concentrations measured in total plasma and in different lipoprotein fractions. In conclusion, within the short duration of observation of this study, our findings demonstrate that insulin resistance and lipoprotein abnormalities associated with PCOS are not secondary to hyperandrogenemia. The clinician, therefore, must be cognizant of the persistence of these metabolic risk factors for cardiovascular disease once successful ovulation and fertility is restored, and institute appropriate monitoring, counseling, and medical intervention as required.

Xenogeneic transplantation of ovarian cortex into an immunodeficient animal host may be an approach toward fertility preservation for young female patients undergoing cancer therapy. Our objective was to evaluate the development of follicles in human ovarian cortex placed s.c. in non-obese diabetic-severe combined immune deficiency (NOD-SCID) mice (n = 54). The following variables were compared: 1) male versus female mice as hosts, 2) intact versus pituitary down-regulated mice, and 3) warm versus cold tissue transport. After 2 wk, 37 of 50 (74%) of the human xenografts contained follicles. At 12 wk after transplantation, exogenous gonadotropin stimulation resulted in follicle growth in 19 of 37 (51%) of the grafts, including the development of antral follicles, which could be palpated and visualized through the mouse skin. Significantly more developing follicles were identified in male versus female mice (13 of 17 vs. 6 of 20, respectively; p = 0.013) after stimulation. No difference was found between intact and pituitary down-regulated mice as hosts. Follicular survival was significantly increased by warm versus cold tissue transport. Our results suggest that s.c. ovarian cortex xenografting into NOD-SCID mice is feasible. Primordial follicles in ovarian xenografts retain their developmental potential and form antral follicles following gonadotropin stimulation.

Objective: Our aim was to assess the effect of the day of ovum retrieval on outcome in an IVF program scheduled for weekday-only ovum retrievals., Design: This was a retrospective study of patients who underwent transvaginal ultrasound-guided ovum retrieval (TVUS-OR) in an IVF program from August 10, 1992, to April 30, 1993., Setting: A university-based tertiary referral hospital center was the setting., Participants and Methods: All patients (n = 501) who underwent TVUS-OR were divided into three groups: (1) patients who underwent TVUS-OR on Monday; (2) patients who underwent retrieval on Tuesday, Wednesday, or Thursday; and (3) patients who underwent retrieval on Friday. All patients were induced by the same controlled ovarian hyperstimulation protocol, which consisted of a GnRH analogue "flare-up" followed by parenteral menotropins, after a scheduled oral contraceptive-induced menses. Patients and cycle characteristics in the three groups were compared and clinical outcome was evaluated., Results: The similarity of patients and cycle characteristics confirmed the uniformity of the three groups. No difference was found in any of the clinical outcomes. However, in the first half of the program, we revealed a trend in which patients at high risk for ovarian hyperstimulation syndrome, requiring freezing all embryos and not allowing transfer during the treatment cycle, occurred more commonly in women whose retrieval occurred on Monday. This trend disappeared in the second half of the analysis., Conclusions: In an in vitro fertilization program in which ovum retrievals occurred only on weekdays, no significant difference in outcome was found in patients undergoing ovum retrieval on Monday or Friday versus midweek. In addition to significant savings by eliminating weekend retrievals, IVF outcome is not compromised.

Maternal virilization in pregnancy is associated, in most benign cases, with luteoma of pregnancy and hyperreactio luteinalis. Only a few reports relate this phenomenon to hyperthecosis or polycystic ovarian syndrome (PCOS). A case of recurrent maternal virilization during two consecutive pregnancies in a patient with PCOS is presented. In both pregnancies, the deepening of her voice, facial hirsutism and scalp hair loss began at the end of the first trimester and regressed 3-4 months post-partum. The patient underwent ovarian venous catheterization, and androgen secretion from both ovaries was found to be markedly high but similar, therefore ruling out an ovarian androgen-secreting tumour. Reviewing the English literature of similar cases, we found reports of only seven cases of maternal virilization during pregnancy associated with PCOS. Here, we present a case of recurrent maternal virilization in pregnancy associated with PCOS.

Objective: To compare oocyte maturity, fertilization rate and cleavage rate after a short and long GnRH agonist (GnRH-a) stimulation protocol and intracytoplasmic sperm injection (ICSI)., Design: Retrospective study of 34 sequential ICSI cycles stimulated with a short or long GnRH-a protocol., Setting: A university-based tertiary care center for assisted reproductive treatment., Results: Significantly more oocytes were mature (metaphase II) after a long GnRH-a protocol then after a short GnRH-a protocol (25.6% and 80.8%, respectively). The long protocol resulted in more cleaving embryos (36/152 versus 9/132) and more cycles of ET (12/17 versus 5/17) than the short group., Conclusion: A greater percentage of mature oocytes results from ovarian stimulation with a long GnRH-a protocol than a short GnRH-a protocol. Maturity could be assessed accurately after cumulus stripping that is required before ICSI. Fertilization rate and cleavage rate with ICSI was superior after a long GnRH-a stimulation protocol for superovulation.

Objective: To explore the pulsatile-release characteristics of LH and P in women with premenstrual syndrome (PMS) compared with age-matched phase-matched controls., Design: Prospective, repeated measures, two-group study., Setting: Human volunteers in an academic research environment., Participants: Six women with rigorously defined prospectively determined PMS; six age-matched phase-matched controls., Main Outcome Measures: Frequency, amplitude, concentration, and coincident pulsatile release characteristics of LH and P at three symptom-related points of the luteal phase., Results: No significant between-group differences in frequency, amplitude, or concentration were found. In pooled data, significant coincident pulsing between LH and P was demonstrated. The length of time between LH and P pulses systematically increased across the luteal phase, a finding not previously reported. In the PMS group only, significant coincident pulsing occurred at an unexpected zero time lag on the symptom-onset sampling day., Conclusion: A progressively increasing coupling interval may reflect the gradual decline of the corpus luteum. Presence of a zero time lag between LH and P at symptom onset in women with PMS may indicate an aberrance in corpus luteum response to LH stimulation.

Objective: To assess the outcome of standard IVF treatment (nonmicromanipulated) with respect to total motile sperm number recovered by swim-up, particularly for couples with severe male factor infertility defined as total motile sperm number < 0.5 x 10(6)., Design: Retrospective study of patients who underwent successful oocyte retrieval in an IVF program from August 10, 1992 to December 31, 1993., Setting: A university-based tertiary referral center (The Toronto Hospital)., Patients: All cycles (n = 672) were divided into four groups according to total motile sperm number recovered using standard swim-up: group 1, total motile sperm number < or = 0.50 x 10(6); group 2, total motile sperm number between 0.51 and 1.00 x 10(6); group 3, total motile sperm number between 1.01 and 1.50 x 10(6); and group 4, total motile sperm number > or = 1.51 x 10(6). All patients received the same controlled ovarian hyperstimulation protocol, which consisted of a GnRH analog flare-up followed by parenteral menotropins. Clinical and cycle characteristics in the four groups were analyzed and outcome was evaluated., Results: There was no significant difference in clinical and cycle characteristics between the groups. The uniformity of the groups justified analysis of their outcome. A fertilization rate of 21.5% was achieved in couples with severe male factor (group 1). Fertilization rate and number of embryos transferred increased directly with the total motile sperm number. There was no significant difference in implantation rate per embryo between the groups., Conclusions: The results in couples with severe male factor infertility compare favorably with monospermic fertilization rates reported in the literature using partial zona dissection and subzonal insertion but is lower than with intracytoplasmic sperm injection. Therefore, we believe that couples with severe male factor infertility should be considered for standard IVF, as long as adequate total motile sperm can be recovered (100 x 10(3) per dish). If intracytoplasmic sperm injection is available, it should be offered to these couples.

Approximately 15% of all couples suffer from infertility, and in 10% of cases, anovulation or oligoovulation is a factor. One of the most common clinical syndromes in which anovulation occurs, often presenting as infertility, is the polycystic ovary syndrome (PCOS).

Objective: To assess adhesion formation after laparoscopic ovarian cautery in women with polycystic ovarian syndrome (PCOS) and the efficacy of Interceed Adhesion Barrier (Ethicon, Summerville, NJ) in their prevention., Design: Prospective, randomized, blinded, clinical study of laparoscopic ovarian cautery with application of Interceed to one ovary, followed by short interval second-look laparoscopy, scoring of adhesions, and clinical follow-up., Setting: Tertiary care clinic at a University teaching hospital., Patients: Eight infertile women with PCOS who failed to conceive with previous clomiphene citrate (CC) therapy., Results: Periovarian adhesions of varying severity developed in all women after laparoscopic ovarian cautery. Interceed showed no protective effect. Despite this finding, all women initiated regular menses after laparoscopic ovarian cautery and seven of eight women spontaneously conceived eight singleton pregnancies without any further therapy., Conclusion: Laparoscopic ovarian cautery should be considered in infertile women with PCOS who fail to respond to CC therapy. These women must be counseled with respect to the possible complication of postoperative adhesion formation.