Is a day 7 blastocyst predictive of the reproductive potential of sibling day 5 and day 6 blastocysts?

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.

Building Healthy Babies: A Mixed-Methods Needs Assessment for a Pre-Conception Program in Ontario.

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.

Patients' and providers' perspectives on the decision to undergo non-urgent egg freezing: a needs assessment.

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.

Deep learning analysis of endometrial histology as a promising tool to predict the chance of pregnancy after frozen embryo transfers.

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.

Patients' and providers' perspectives on non-urgent egg freezing decision-making: a thematic analysis.

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.

The effect of the Ontario Fertility Program on IVF utilization and outcomes in women of advanced reproductive age.

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%.

Anti-mullerian hormone (AMH) reference values in the CALIPER cohort of healthy community children and adolescents.

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.

Endometrial laminin subunit beta-3 expression associates with reproductive outcome in patients with repeated implantation failure.

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.

Cargo small non-coding RNAs of extracellular vesicles isolated from uterine fluid associate with endometrial receptivity and implantation success.

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.

Comparing endometrial receptivity array to histologic dating of the endometrium in women with a history of implantation failure.

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.

Safety and Assisted Reproductive Technology Outcomes of Hysteroscopic Tubal Microinserts Versus Laparoscopic Proximal Tubal Occlusion or Salpingectomy for Hydrosalpinges Treatment.

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.

Survey of Third-Party Parenting Options Associated With Fertility Preservation Available to Patients With Cancer Around the Globe.

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.

Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe.

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.

Expanding Urgent Oncofertility Services for Reproductive Age Women Remote from a Tertiary Level Fertility Centre by Use of Telemedicine and an On-site Nurse Navigator.

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.

BRCA1 Mutation Status and Follicular Fluid Exposure Alters NFκB Signaling and ISGylation in Human Fallopian Tube Epithelial Cells.

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.

Progesterone, progesterone/estradiol and ART outcomes in day-5 transfer cycles.

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.

Unexplained Infertility and Undiagnosed Celiac Disease: Study of a Multiethnic Canadian Population.

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.

Altered expression of inflammation-associated genes in oviductal cells following follicular fluid exposure: implications for ovarian carcinogenesis.

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.