Ahmad AlMalki, Armand Zini
McGill University, Montreal, QC
Ahmad AlMalki1, Armand Zini1, Simon Philips2
1McGill University, Montreal, QC; 2Ovo Clinique, Montreal,QC
Virginie Arpin, Noémie Beaulie,Katherine Péloquin
University of Montreal, Montreal, QC
Infertility and its treatments not only affect individual functioning, but also relationship functioning. Studies have shown that individuals seeking fertility treatments reported poorer relationship satisfaction and higher level of relational stress (Sundby et al., 2007; Wang et al., 2007; Zhang et al., 2000). Research showed that interventions which have been developed to address distress experienced by women and couples undergoing fertility treatments, whether individual and couple therapy, or group interventions, are helpful in reducing distress (psychiatric symptoms and marital distress) (Boivin, 2003; De liz et Strauss, 2005; Hussein, 2014). In her review of the literature, Boivin (2003) found that the most effective interventions lasted between 6 and 12 weeks, had a strong educational focus on medical knowledge and skills training (e.g., stress management skills). Previous intervention studies often presented important limits (Hämmerli et al., 2009): group interventions were often targeting women and IVF treatment only, and the majority of interventions were spread over less than 5 sessions. Peloquin and Brassard (2013) developed a new psychoeducational and support group-based intervention, which addressed the limits raised by Hämmerli et al. (2009) and followed Boivin’s recommendations. The current study examined whether this new group-based intervention (Peloquin, 2013) is effective in reducing infertility-related relationship distress in 11 men and 14 women seeking various fertility treatments. They completed baseline questionnaires individually via an online secure web platform one week before the beginning of the intervention, took part in the 6 bi-monthly sessions, and completed post-intervention questionnaires. Measures included the Dyadic Adjustment Scale (DAS; Spanier, 1976; Sabourin et al., 2005), Fertility quality of life questionnaire (FertiQoL; Boivin et al., 2011), Marital Benefits scale (Schmidt et al., 2005), and the Fertility Problem Inventory (FPI; Newton et al., 1999). Repeated-measures t-test analyses showed a reduction in FPI relationship concern (t(21) = 2.13, p = 0.45) and an increase in quality of life related to the relational domain (t(24) = 2.28, p = 0.32) and marital benefits (t(24) = 2.47, p = 0.21) following the intervention. Overall relationship satisfaction (DAS) did not change following the intervention. This preliminary study suggests that a psychoeducational support group might be useful in addressing the relational impacts of infertility and its treatments, beyond individual psychological distress.
Amal Zamal1 , Ahmad Alsanei1 , Serdar Coskun1,2, Khalid Awartani1,2
1 King Faisal Specialist Hospital & Research Centre, Saudi Arabia; 2 AlFaisal University, Collage of Medicine, Saudi Arabia.
Following IVF treatment, patients are routinely given progesterone supplementations for luteal phase support. In our program it is given for an average of 8 weeks in form of either Intramuscular progesterone 50mg daily injections, or vaginal cyclogest suppositories 400mg BID based on patient’s preference. We observed patients demand on more IM preparations, while there is a worldwide shortage in supply of the IM progesterone. The objective of our study is to assess the patient’s preference regarding the routes of progesterone supplementation and their satisfaction with the selected choice, and Compare the efficacy of the different routes.
Prospective cohort study, patients < 40 years old undergoing IVF treatment at our clinic were offered to participate. Patients were allocated by their choice to either group A (the vaginal progesterone), or group B (IM progesterone). Both groups were treated similarly apart from the progesterone intervention. A satisfaction score from 1-5 was used to assess patients satisfaction in regard to the treatment method, they were interviewed for recording of their satisfaction and the side effects. Sample size was calculated for a total of 409 patients.
227 patients (55.5%) were in (group A) and 182 patients (44.5%) were in (group B). Average age and BMI was similar in both groups. 33.5% of the patients in group A and 29% of the patients in group B had reported at least one side effect, P=0.3. The most common side effect for group A was vaginal leak 15% of all women having cyclogest, the most common side effect in group B was discomfort after administration 18% of all patients who had Injections. The median satisfaction score for group A was 5 and for group B was 4, P=0.13. The pregnancy rate for group A was 38.8% and 34% for group B
This initial data showed that almost half of the patient undergoing IVF treatment have selected IM progesterone for luteal phase support, there was more significant difference in the patient’s satisfaction, at second visit toward the geston group. No significant difference in the side effect and pregnancy rate in both groups.
Agata Sojecki1, Gelareh Motamedi1, Hanna Balakier1,Clifford Librach1,2,3
1CReATe Fertility Centre, Toronto, ON; 2Departments of Obstetrics & Gynaecology and Physiology, University of Toronto, ON; 3Department of Gynaecology, Women’s College Hospital, Toronto, ON
Blastomere multinucleation (MN) is a common nuclear abnormality observed in early human embryos and is considered abnormal. Early FISH reports indicated that some aneuploid embryos may be capable of ‘self-correction’ during development to the blastocyst stage, which suggests the existence of repair mechanisms which could restore them to normal ploidy. The aims of the present study were to: use a time-lapse incubation system to compare the morphokinetics and developmental potential of human embryos with, and without, MN; and re-evaluate the relationship between MN and embryo ploidy status using contemporary PGS methodologies.
Materials and Methods
This study was approved by the Research Ethics Board of the University of Toronto. Rate of multinucleation at the 2- and 4-cell stage (MN2 & MN4), time-lapse morphokinetic parameters from zygote to blastocyst stage, ploidy of embryos analyzed by trophectoderm biopsy followed by array comparative genomic hybridization (CGH), and pregnancy outcomes were collected.
A total of 1055 out of 2441 (43.2%) embryos evaluated by the Embryoscope™ showed blastomere multinucleation at the 2-cell stage. The rate of multinucleation was significantly reduced (357/2441; 15.0%) at the 4-cell stage. The timing of cleavage divisions from the pronuclear fading to 5-cell embryo (tPNf to t5) were significantly longer (1.0-2.5 h) in MN 2 embryos than in non-MN2 controls (P<0.001). MN4 embryos compared to non-MN4 controls had a significantly longer pronuclear fading time, time to reach the 2-cell stage (3-40 minutes), and spent a prolonged time in the 4-cell stage (1.5h; P<0.001). Of the total embryos tested with PGS (n=607), the rate of MN was similar in euploid vs. aneuploid blastocysts (40.8% and 46.7% respectively, P = 0.209). Both euploid (78%) and aneuploid (57%) MN2 embryos showed nuclear correction by cleaving into entirely mononucleated 4-cell stage embryos. There were 61 transfers of MN2 embryos that resulted in 45.9% clinical pregnancies and a 31.6% implantation rate.
The frequency of multinucleation is high in early cleavage stage human embryos, and there is no difference in frequency between those embryos found to be euploid or aneuploid at the blastocyst stage of development. Our data suggests that most MN embryos have the capacity for self-correction during early cleavage divisions, and can develop into euploid blastocysts and clinical pregnancies.
Magdalena Bielanska, Dianne Hoppe, and Marie-Claude Léveillé
Ottawa Fertility Centre, University of Ottawa, Ottawa, ON
Introduction: Purell ®Advanced Hand Rub is an instant hand sanitizing gel containing both 70% ethyl alcohol and iso-propanol. Oxivir ® Plus is a one-step cleaner and high level disinfectant for hard non-porous surfaces, containing accelerated hydrogen peroxide (AHP®) technology. Both products have been recommended by health authorities for use in operating rooms and laboratories. In order to determine whether these products are safe to use in an IVF clinic, we analyzed the impact of volatile organic compounds (VOCs) from Purell and Oxivir on mouse embryo culture.
Materials and Methods: Modular incubator chambers were used to expose embryo culture media and oil (G1-Plus, G2-Plus, and OVOIL; Vitrolife) to VOCs from Purell ®Advanced Hand Rub, from Oxivir® Plus (1:40 working dilution) and from sterile water (Baxter; control). The total VOC levels emitted by each product was quantified using a VOC probe (GrayWolf Sensing). A total of 180 one-cell mouse zygotes were warmed and randomized into 3 treatment groups: Purell, Oxivir or Water (control) and cultured in respective pre-conditioned media under oil, in a standard clinical tri-gas incubator 37 °C, 6% CO2, 5% O2. Embryos were scored at 24, 72, 96 and 120 hrs of culture.
Results: The VOC readings after a 4 min and after 1 hr of exposure of probe to each product were 23000 ppb and 23331 ppb (Purell), 7690 ppb and 1100ppb (Oxivir), and 20 ppb and 20 ppb (Water). While development to the blastocyst stage did not appear to be affected by exposure of culture media to Oxivir, exposure to Purell resulted in 93% of zygotes degenerating by 24 hrs and the other 7% blocking at the 1-cell stage.
Conclusions: Ingredients of Purell Hand Rub cause an immediate marked rise in VOCs. Mouse experiments indicate that while the use of Oxivir is not detrimental to embryo development to the blastocyst stage, use of Purell can lead to drastic loss of zygotes. Until further studies using human gametes prove otherwise, the use of Purell hand sanitizer in an IVF clinic, particularly in areas where gametes and embryos are collected, manipulated or cultured is not recommended.
Lauren Beliveau1 *, Angelos Vilos1 , Francis Tekpetey2 , Karen Shepherd2 , Chris Newton2 , Basim Abu Rafea1 , Jackie Hollett-Caines1 , Maggie Rebel1
1 Department of Obstetrics and Gynecology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON; 2 The Fertility Clinic, London, ON
Introduction: Controlled ovarian hyperstimulation (COH) together with intrauterine insemination (IUI) is commonly offered to couples with subfertility factors not involving the fallopian tubes. Several studies have examined factors leading to IUI success but none to date have specifically set out to examine the effects of the number of lead follicles on pregnancy outcomes, live birth rates, and the rate of multiples. The aim of our study was to assess the impact of the number of lead follicles at the time of trigger on pregnancy and live birth rates after undergoing COH/IUI.
Materials and Methods: A retrospective study of all patients undergoing IUI at The Fertility Clinic in London, Ontario, Canada from January 2009 to January 2014 was undertaken. 1350 IUI cycles using gonadotropins alone were performed in the 5-year period. Lead follicle size was determined to be 16mm or greater. IUI was performed approximately 36 hours after triggering ovulation. Outcomes examined were clinical pregnancy, live birth, and multiple pregnancy rates. Other factors assessed were female age, body mass index (BMI), cause of infertility, day 3 FSH, and total motile sperm count (TMC).
Results: The number of lead follicles ranged from 0 to 5. 1321 cycles (97.9%) achieved 1, 2 or 3 lead follicles. Positive BhCG on luteal day (LD) 18, positive fetal heartbeat on LD40 ultrasound, and live birth rates were 18.8%, 13.5%, and 12.7% for one lead follicle; 26.8%, 21.1%, and 19.5% for two lead follicles; and 27.4%, 22.6%, and 21.7% for three lead follicles respectively. All three rates were significantly higher with two compared to one lead follicle (P
Conclusion: Our study demonstrated significantly better pregnancy and live birth outcomes with an acceptable multiple rate in cycles of COH/IUI attaining two lead follicles compared to one. This provides valuable information for counseling patients undergoing IUI.
Lauren Beliveau1*, Angelos Vilos1 , Stan Van Uum2 , Chris Newton3 , Gideon Koren4 , George Vilos1 , Steve Power1 , Jackie Hollett-Caines1 , Maggie Rebel1 , Basim Abu Rafea1
1 Department of Obstetrics and Gynecology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON; 2 Department of Endocrinology and Metabolism, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON; 3 Department of Psychology, The University of Western Ontario, London, ON; 4 Department of Clinical Pharmacology, University of Toronto, Toronto, ON
Introduction: Chronic stress has been linked to reduced fertility and even poor pregnancy outcomes. Hair cortisol sampling has emerged as a novel method for examining stress over longer periods of time. Our study set out to determine if hair cortisol levels were increased in infertile women as compared to fertile control subjects.
Materials and Methods: With REB approval, sixty women were enrolled from April 2013 until April 2014. Thirty patients who had not conceived within the past year and were seeking IVF treatment served as the cases. Thirty age matched patients with proven fertility acted as our controls. All study patients were assessed for overall stress using the Perceived Stress Scale (PSS). In addition, infertile women were given the Fertility Problem Inventory (FPI), a survey measuring perceived infertility-related stress. Hair samples were taken for cortisol measurements using standard protocols.
Results: Mean hair segment 1 (0-3cm) and 2 (3-6cm) cortisol levels (ng/g) in the infertility group were 111 +/- 135 and 121 +/- 194 respectively; and in the control group were 173 +/- 231 and 112 +/- 147 respectively. The results showed no significant difference in overall cortisol levels in hair samples between infertile women and controls. The infertility group, however, reported significantly higher levels of stress than controls on the PSS (t= 2.6, P= .012). There was also no significant relationship found between FPI Global scores and cortisol levels in the infertility population. On the FPI, 37% of the infertility group scored above the 84th percentile compared to fertility norms, correlating with “moderately high” infertility related stress. Of these, 3.3% had scores above the 98th percentile, indicating “very high” stress. In the infertility group, there was a significant but moderate correlation between the PSS total score and the FPI Global score (r= 0.41, P= .025).
Discussion: Cortisol levels in both groups were highly variable as shown in the large standard deviations. The small sample size may mask the true differences found in cortisol levels between the control and infertile female patients. Nonetheless, our study reaffirms the high level of perceived stress experienced by women dealing with infertility. This emphasizes the need to expand this body of research to aid in development of stress reduction strategies in the infertility population.
Yaakov Bentov1 , Andrea Jurisicova2
1University of Toronto, OBGYN/REI, Trio fertility, Toronto, ON; 2University of Toronto, OBGYB/REI, LTRI MSH, Physiology Department, Toronto, ON
Metformin is the most widely used medication for the treatment of type II diabetes. More recently it has been broadly adopted for the treatment of PCOS prior and during pregnancy. However, despite decades of clinical use, it was only recently shown that most of the actions of metformin are mediated via inhibition of the first complex of the mitochondrial electron transport chain and more specifically via inhibition of the reduction of the electron carrier, ubiquinol. Inhibition of the electron transport chain induces a state of low energy that in turn activates the energy sensor protein AMPK. The low energy state of the cell sensed by AMPK activates catabolic reactions and inhibits anabolic biochemical reactions such as gluconeogenesis, the main anti diabetic action of the drug. The oocytes and early embryos are dependent on mitochondrial ATP and are extremely sensitive to disturbances in mitochondrial function. In addition, several recently published studies both in animals and humans suggest that exposure to metformin in utero may reprogram the offspring’s metabolism and increase the risk for developing the metabolic syndrome later in life.
The aim of the study was to compare mitochondrial function and metabolism in granulosa/cumulus cells which were cultured with or without metformin
We incubated granulosa and cumulus cells from ICR mice that were fed on a regular diet in culture media with or without Metformin. Later we measured the cellular ATP concentration (Cell Titer Glo, Promega;ADP/ATP ratio, ApoSensor, BioVison) and compared it between the cells.
Granulose – cumulus cells from female ICR mice that were cultured with Metformin had shown a 25% decline in cellular ATP concentration in comparison with granulosa-cumulus cells cultured with no metformin.
These preliminary results suggest that under physiologic Metformin concentration granulosa -cumulus cells that reflect the metabolism of the oocyte, have a decreased capacity to produce energy. In this stage of its development both the oocyte and young embryo are totally dependent on mitochondrial energy and are very sensitive to changes in its availability. We will conduct more tests of the cumulus oocyte complex for other mitochondrial markers, synthetic capacity and gene expression both in mice and humans to further estimate the effect of exposure to physiological metformin concentration on the function of these cells.
Paul Bingil1, Joanna Greer1, Michael Crowe1, Thomas G.Hannam2, William B. Schoolcraft3, Jason E. Swain4,Alexander Lagunov1
1CCRM Toronto, Toronto ON; 2Hannam Fertility Centre,Toronto, ON; 3Colorado Centre for Reproductive Medicine,Lone Tree, CO; 4CCRM IVF Network, Lone Tree, CO
IVF patients are often counseled to have their embryos warmed by the laboratory where they were cryopreserved to avoid potential issues with transportation, discrepancy of freeze/thaw protocols, unfamiliarity with novel storage devices, communications with the patient, etc. However, despite the risks, transport of embryos to another laboratory for use is often required. Implementation of a detailed gamete transport/receiving procedure is critical to minimize the risk and maximize the pregnancy rate of embryos cryopreserved in external laboratories.
A retrospective analysis of data from November 2014 – November 2015 was performed, examining cell survival and pregnancy outcomes of all non-CCS Frozen Blastocyst Transfers (FBT) cycles derived from cryopreserved embryos shipped from external laboratories (n=62) versus those frozen “in-house” (n=88). For 59 cases in the external group, a variety of vitrification methods were used, including the Cryolock, HSV and Fast-Freeze and slow-rate cooling methods in 0.25cc straws. In-house embryos were all vitrified using the Kitazato Cryotop. Two groups were compared on the basis of cell survival (CS) and Chemical pregnancy rate (CPR). A single courier was used for all transportation logistics. Fisher’s exact test used for statistical correlations. (P<0.05)
Though not statistically significant (p= 0.369, 0.176), a trend towards higher pregnancy rate was observed with the in-house embryos. There was also no statistical difference in the average survival amongst the groups.
Embryos cryopreserved at external laboratories can yield acceptably high survival and resulting pregnancy rates if transported/warmed by another laboratory. This requires a well-controlled gamete shipping/receiving system consistent with proper communication and coordination with external clinics and internal resources to ensure proper/timely sample delivery, inventory assessment, stocking of appropriate media and possible training/review of novel warming protocols in advance to avoid issues with patient samples. With these factors considered, the quality of shipped-cryopreserved embryos can be maintained.
Kristy Cho1, Caitlin Dunne1,2, Angel Shan1, Jennifer Hutcheon3, Ursula Smith Durland2, Ken Seethram1,2, Jon Havelock1,2
1University of British Columbia, Department of Obstetrics &Gynaecology, Division of Reproductive Endocrinology and Infertility, Vancouver, BC; 2Pacific Centre for Reproductive Medicine (PCRM), Burnaby, BC; 3University of British Columbia,Department of Obstetrics and Gynaecology, Division of Maternal-Fetal Medicine, BC
During controlled ovarian stimulation (COH) for in vitro fertilization (IVF) supraphysiologic levels of estradiol (E2) have been associated with poor placentation and adverse pregnancy outcomes (1,2). This study aimed to investigate whether high peak E2 on day of hCG trigger is associated with low PAPP-A and ultimately adverse perinatal outcomes.
Methods and Material:
This is a retrospective longitudinal cohort study including 216 patients with a singleton pregnancy after fresh embryo transfer who also underwent first trimester screening (FTS) at a private, university-affiliated fertility centre in Vancouver, Canada.
High serum estradiol (≥13 035 pmol/L) at controlled ovarian stimulation was not correlated with low PAPP-A ( 0.05). High peak E2 was not associated with a total composite of maternal and neonatal adverse birth outcomes (p = 0.30). 36 of 174 pregnancies in the normal E2 group (21%) had an adverse outcome compared with 12 of 41 in the high E2 group (29%). As internal validation, our cohort did show a correlation between low PAPP-A (
Our results do not support the theory that high estradiol at fresh embryo transfer impedes placentation. We found no association between high estradiol and subsequently low PAPP-A levels or adverse pregnancy outcomes.()Table. Maternal and neonatal birth outcomes for normal and high E2 groups.
1 Giorgetti C, Meerschaut FV, De Roo C, Saunier O, Quarello E, Hairion D, et al. Multivariate analysis identifies the estradiol level at ovulation triggering as an independent predictor of the first trimester pregnancy-associated plasma protein-A level in IVF/ICSI pregnancies. Hum Reprod 2013; 28(10):2636–42.
2 Imudia ANA, Awonuga AOA, Doyle JOJ, Kaimal AJA, Wright DLD, Toth TLT, et al. Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization. Fertility and Sterility 2012; 97(6):1374–9.
Erin Crosley1, Ursula Durland2, Jeffrey Roberts2, Cheryl Portigal-Todd3, Kristin Turner3
1University of British Columbia, Genetic Counselling Program, Vancouver, BC; 2Pacific Centre for Reproductive Medicine, Burnaby, BC; 3BC Cancer Agency, Vancouver,BC
Introduction: Previous work has shown female cancer patients of reproductive age to be significantly less likely to receive fertility preservation (FP)-related information at the outset of cancer diagnosis and treatment than their male counterparts. Research shows that barriers such as lack of knowledge on both the side of the patient and the health professional impede FP discussions from taking place. The objectives of this study were to a) develop an informational tool for professionals and b) interview professionals to gather insight into barriers around FP and solicit feedback on the informational tool.
Materials and methods: An informational tool was designed following CFAS and ASCO clinical practice guidelines. Qualitative data were collected using semi structured interviews with 6 physicians practicing at a major cancer center in Vancouver, British Columbia.
Results: All participants self-reported as personally having discussions about FP with patients. The major themes that emerged from qualitative analysis included barriers to FP (namely timing, cost, and physician knowledge and comfort), professional approaches to discussing FP with patients, as well as professional perspectives on the patient experience. While participants did not feel provision of an FP tool would increase the likelihood of FP discussions taking place, they felt it may improve the quality of the discussions. Feedback on the informational tool included adding disclaimers to procedural descriptions and making the tool an online resource. Participants also felt the FP tool could serve as a patient resource.
Conclusions: FP discussions and referrals are taking place at a relatively high rate at one major care center in Vancouver. Provision of an informational tool may be helpful in facilitating FP discussions with patients.
Michael Crowe1, Joanna Greer1, Paul Bingil1, Thomas G. Hannam2, William B. Schoolcraft3, Jason E. Swain4, Alexander Lagunov1
1 CCRM Toronto, Toronto ON; 2 Hannam Fertility Centre, Toronto, ON; 3 Colorado Centre for Reproductive Medicine, Lone Tree, CO; 4 CCRM IVF Network, Lone Tree, CO
With the success of vitrification and high cell survival rates, additional measures and techniques to further improve upon outcomes are desired. Assisted hatching (AH) is a method commonly employed in attempts to improve success of IVF by facilitating the escape of the embryo from the zona pellucida. The aim of this study was to assess the impact of AH on the survival/expansion of thawed blastocysts and resulting pregnancy rates.
A retrospective analysis was performed of patients who had undergone frozen blastocyst transfer (FBT) (n=76; 35.3 years +/- 3.2), after vitrification of good quality blastocysts (>3BB). Group A (n=17, avg age=34.7 years) included embryos where no AH was performed upon warming and Group B ( n=59, avg age=35.1 years) included embryos undergoing AH. Donor egg and CCS cycles were excluded. Day 5/6 blastocysts were vitrified/thawed using an in-house proprietary media and methodology – combined with the Kitazato Cryotop system. Thawing was performed on the day of FBT a minimum of two hours prior to transfer. Assisted hatching in Group B was performed immediately after warming using an Active Saturn V5 laser (RI Instruments) using a 20um hole. Cell survival upon thaw, expansion immediately prior to transfer (0= no expansion, 1= slight expansion 0-30%, 2= medium expansion 30-70%, 3= full expansion 70-100%), and subsequent chemical pregnancy rates were recorded. Data were analyzed using Fisher’s exact test, p<0.05)
Cell survival and re-expansion after warming remained comparable across both groups, indicating no adverse effect of AH. Chemical pregnancy in Group A (no AH) was not significantly different than group B, suggesting no benefit of AH (p=0.7750)
A high degree of blastocyst expansion (2-3) in both groups was directly related to increased pregnancy rates, which highlights the importance of re-expansion upon thawing prior to embryo transfer. Poor or no expansion, even after excellent cell survival at thaw, yielded very poor pregnancy rates.
A more informative measure of blastocyst survival, such as blastocoel expansion, may be more insightful than simple assessment of intact cells upon warming. This may require additional culture time in the lab between warming/transfer to assess. High quality blastocysts with good survival upon thaw can result in high rates of pregnancies regardless of AH being performed, as long as significant expansion has occurred prior to embryo transfer.
Dylan Cutler1, Anthony P. Cheung1,2
1University of British Columbia, Vancouver, BC; 2Grace Fertility Centre, Vancouver, BC
Introduction: Polycystic ovary syndrome (PCOS) is a multisystem endocrine disorder affecting between 5-15% of women worldwide. Increased caloric intake and sedentary lifestyle are thought to contribute to obesity and insulin resistance in PCOS but the roles of dietary composition are less clear. We hypothesized that dietary macronutrient composition was related to insulin resistance in women with PCOS.
Methods: Women with PCOS and regularly ovulating women who presented with infertility were recruited for this cross-sectional study. Three-day food and activity diaries were completed by 62 women with PCOS and 32 normal ovulating women (respective mean age ± SEM: 32.3 ± 0.66 vs. 36.4 ± 0.94, and BMI: 28.3 ± 0.82 vs. 23.4 ± 0.77). Outcome measurements such as dietary intake, physical activity, anthropometric and metabolic characteristics (fasting blood glucose, 2 hour oral glucose tolerance test (OGTT), and fasting insulin) of women with PCOS were compared to normal ovulating women. Group differences were compared using Student’s t tests or Mann-Whitney tests according to data normality, while correlation was assessed using Spearman’s Rank tests.
Results: Women with PCOS consumed significantly less fibre (P = 0.004, medians: 20 vs. 24 grams, respectively) than normal ovulating women. No differences were found between protein, fat, carbohydrate or overall caloric intakes. Among women with PCOS, those with abnormal OGTT consumed significantly less fibre (P = 0.004, medians: 17 vs. 22 grams) and less calories (P = 0.06, medians: 1790 vs. 1875 kilocalories, respectively), but protein, carbohydrate and fat intake were similar to those with normal OGTT. Fasting insulin correlated negatively with fibre (r = -0.50, P = 0.001). BMI and WHR had no correlations with dietary components.
Conclusions: This is the first study to identify habitual fiber intake as a possible factor in glucose intolerance in women with PCOS. These findings suggest insufficient dietary composition, more so than increased caloric intake, may exacerbate insulin resistance in women with PCOS.
Judith C. Daniluk, Emily Koert
University of British Columbia, Vancouver, BC
The need to delay childbearing past what they believe is the ideal age to start a family is a reality for many women who hope to have children. Previous research has shown that career and educational aspirations, financial stability, personal readiness, and partner availability and readiness are salient factors in the decision to postpone childbearing. This study was conducted to determine if age, relationship status and economic circumstances are related to women’s childbearing intentions and beliefs, and to the factors women feel are most salient in the timing of becoming a mother.
Material & Methods:
A cross-sectional survey was conducted of 500 Canadian childless women, ages 18 to 38 years, who presumed they were fertile and were open to the possibility of a pregnancy in the future. Respondents completed an online, self-report questionnaire assessing their fertility intentions and beliefs, and identifying the factors they felt were important in the timing of childbearing.
Respondents expected that they would have their first child child around age 31, despite believing that it would be ideal to have a child at 27. There were significant differences in women’s fertility intentions based on age but no significant differences based on relationship status or income except for women from lower incomes reporting a higher latest age for childbearing. Women rated being able to financially support a child, being in a stable relationship, and having a partner who would be an involved and loving parent as the most important factors in the timing of motherhood. Completing their education was very important prior to having children for younger women (P=.005), single women (P=.005) and higher income women. (P=.045). Younger women also identified being established in their career (P=.010), being young enough and having the energy to be an involved parent (P=.024), and having a proper home in which to raise a child (P=.023) as being more important in their childbearing decisions. Financial stability was particularly important to single women (P=.017) whereas being able to stay home to raise their child was more important to women in the lower income group (P=.036).
The findings demonstrate that age is more salient than relationship or socioeconomic status in women’s childbearing intentions and the factors that women believe are important in the timing of childbearing.
Patrick Davis1 , Santiago Munnè2, Angeline Beltsos3, Katie Bauckman2, Colleen Coughlin4
1Chicago College of Osteopathic Medicine, Downers Grove; IL, 2Reprogenetics Livingston, NJ; 3Fertility Centres of Illinois, Chicago, IL; 4Aparent IVF, Highland Park, IL
Introduction: Preimplantation genetic screening (PGS) of human embryos has offered couples battling infertility and recurrent miscarriage possible answers. It has proven to be a powerful tool in achieving pregnancy resulting in a healthy baby sooner. As the technology advances many methods of PGS have emerged including array comparative genomic hybridization (aCGH) and high-resolution next-generation sequencing (hr-NGS). However, there is little data comparing these two methods of PGS in regards to clinical outcome. This study aims to compare the two methods in order to determine whether PGS performed via aCGH or hr-NGS offer better clinical pregnancy rates or lower miscarriage rates.
Methods: A retrospective analysis was performed to investigate implantation, clinical pregnancy and miscarriage rates among patients who underwent PGS testing at the same fertility center, prior to embryo transfer with either aCGH (n=637) or hr-NGS (n=49). A statistical analysis was then performed using a chi-squared analysis. Data was also collected on patient’s reason for testing, age, D3 FSH, AMH, E2, and number of embryos transferred and evaluated for statistical similarities.
Results: Patient in both groups were found to have statistically similar mean E2, mean BMI and mean number of embryos transferred. However, mean age (aCGH 36 years vs. HR-NGS 34 years, p=<0.001), mean D3 FSH (aCGH 9.3 vs. HR-NGS 7.5, p=0.004), and mean AMH (aCGH 3.5 vs. HR-NGS 7.1, p=<0.001).
PGS performed with aCGH, and hr-NGS resulted in 43% (361/831) and 50% (30/60) implantation rates, respectively (p = 0.323); 48% (303/637) and 55% (27/49) clinical pregnancy rates, respectively (p = 0.309); and 19% (58/303) and 26% (7/27) miscarriage rates, respectively (p =0.396). Therefore, no statistical difference was found in implantation rate, clinical pregnancy rate or miscarriage between tests.
Discussion: As technology advances, hr-NGS has offered an addition method of PGS testing that has been proven to be as reliable as aCGH. NGS also offers the distinct advantage of being able to pick up mosaicism in embryo biopsies, which aCGH is unable to do.
In this study hr-NGS has proven to be as effective as aCGH and provide similar clinical outcomes. It is possible that future more robust studies may be able to demonstrate better clinical result given that fact that hr-NGS can detect mosaicism in embryos and avoiding using potentially abnormal embryos.
Megan Dufton1, Linda Hamilton1, David Mortimer1,2
1 Atlantic Assisted Reproductive Therapies, Halifax, NS; 2 Oozoa Biomedical, Vancouver, BC
Adjuvant treatment using DHEA and/or co-Q10 and/or growth hormone (GH) is becoming increasingly common for patients of advanced maternal age and poor responders. Various studies have suggested that DHEA can increase egg number and improve embryo quality, while GH can improve pregnancy outcome, and both are thought to increase egg quality. Co-Q10 can reduce aneuploidy rates in advanced maternal age patients.
Material and Methods
The impact of GH, DHEA and Co-Q10 was investigated in the next cycle of 33 patients of advanced maternal age or poor responders who had failed to achieve clinical pregnancy in a previous IVF cycle. Paired analyses considered egg number, egg maturity and grade, fertilization rate, blastocyst quality and pregnancy outcome. Egg grading considered cumulus expansion and appearance, expansion of the corona radiata, egg colour and shape. Blastocyst graded considered blastocoel size and the number and adhesion of cells in the both the trophectoderm and the inner cell mass.
Patients had significantly more eggs retrieved in cycles which did not include supplementation (8.4 vs 6.7, P<0.02), although this included significantly more immature eggs (1.8 vs 0.85 P<0.005). The number of good or better grade eggs did not differ between the untreated and treated cycles (6.2 vs 5.3, P=0.153), nor were there differences in either the number of eggs fertilized (3.9 vs 3.6, P=0.604) or the fertilization rate per egg retrieved (47.4% vs 56.6%; P=0.157). The number of good or better grade blastocysts was the same in the untreated and treated cycles (0.2 vs 0.3, P=0.628), and paired analysis revealed no significant difference in the number of poor quality blastocysts available for transfer (1.1 vs 1.5, P=0.296). However, 6/33 patients (18%) had successful pregnancies and live births from their second cycles. Finally, separate analysis of patients who had a first cycle cancelled and then completed a treated cycle, showed that 23.5% (4/17) of these patients had an ongoing pregnancies after their treated cycle.
This study failed to demonstrate that DHEA, growth hormone and co-enzyme Q10 increased egg or embryo quality. Although 18% of the patients achieved a live birth from their treated cycles, random chance could explain these pregnancies.
Leyla Eryuzlu1 , Ekaterina Shlush2 , Clifford Librach2,3,4,5,6 Prati Sharma2
1 Faculty of Medicine, University of Toronto, ON; 2 Department of Obstetrics and Gynaecology, University of Toronto, ON; 3 Department of Physiology, University of Toronto, ON; 4 Institute of Medical Sciences, University of Toronto, ON; 5 Department of Gynecology, Women’s College Hospital, Toronto, ON; 6 CReATe Fertility Centre, Toronto, ON
Polycystic ovarian syndrome (PCOS) affects approximately 6.5-8% of women of reproductive age. Women with PCOS commonly experience infertility, as well as an increased miscarriage rate. PCOS results in an increased number of antral follicles which contributes to higher serum anti-Mullerian hormone (AMH) levels, and thus serves as a highly accurate predictor of ovarian reserve. Older women with PCOS have higher ovarian reserve than age matched women without PCOS. The objective of this retrospective chart review was to determine whether infertile women of advanced reproductive age with PCOS experience an advantage in their response to fertility treatment and pregnancy outcomes compared to non-PCOS infertile advanced reproductive age women.
Materials and Methods
This study received institutional REB approval. Patients were considered eligible if they were: a) 35 years of age or older; and b) received treatment at CReATe Fertility Centre (Toronto, Ontario). Cases were defined as patients with an AMH level ≥ 20 pmol/L; controls were defined as patients with an AMH level of 8-14 pmol/L. Patients with male infertility factor were excluded. Analyses were conducted for all cases and controls, and also stratified by age-group (35-37, 38-40, 41-43, and 44+ years).
Data was collected from 830 patients, of which 420 (50.6%) were cases and 410 (49.4%) were controls. A significantly higher ongoing clinical pregnancy rate was found between cases (n=91; 21.7%) relative to controls (n=65; 15.9%) (P=0.033). Spontaneous abortion rates did not significantly differ between groups (P=0.195).
Women of advanced reproductive age with PCOS appear to have a significantly higher ongoing clinical pregnancy rate than women without PCOS. Our findings suggest that a history of PCOS plays a significant role in predicting the success of fertility treatment in women with advanced reproductive age.
Navid Esfandiari1 , Khalid M. Rao2 , Dennis Dela Cruz1 , Robert F. Casper2
1 Dartmouth Hitchcock Medical Centre, Lebanon, HN; 2 Trio Fertility Centre, Toronto, ON
Objective: Improvement in blastocyst culture and vitrification has resulted in routine cryopreservation of blastocysts with remarkable survival and implantation rates in frozen embryo transfer cycles (FET). Vitrified blastocysts are collapsed upon warming and it is sometimes difficult to assess whether they have survived intact. Generally, blastocysts are cultured for a few hours after warming, and sometimes overnight, to assess re-expansion as an indicator for survival and reproductive potential. We sought to determine if incubation between thawing and transfer to allow blastocyst re-expansion or immediate transfer without incubation influences clinical outcomes of FET with vitrified blastocysts.
Design: Retrospective study in a University of Toronto affiliated infertility program.
Materials and Methods: Six hundred and twenty FET cycles was started between Jan 2013 and December 2014. The blastocysts were vitrified using Kitazato kit and Cryotop vitrification device on day-5 or day-6 of development. The blastocysts were thawed in the morning and transferred after 1-3 hours of incubation in GII-plus culture medium, or immediately after warming in the warming solution. Seven cycles were cancelled because no blastocyst survived. Five hundred and sixteen embryo transfers were performed by 5 staff physicians and 4 REI fellows (group I). One REI provider, with a very busy morning OR schedule, had to complete embryo transfers as soon as the blastocysts were thawed (group II, n=97).
Results: A total of 1036 vitrified blastocysts was warmed and 1003 survived (96.8%). The overall PRs in groups I and II were 39.5% and 56.7%, respectively (p= 0.053). Patient age, number of embryos transferred, and pregnancy outcome between the two groups are shown in table 1. Transferring blastocysts that were vitrified on day-5 resulted in a higher pregnancy rate as compared to day-6 in both groups.
Conclusion: Re-expansion of vitrified-warmed blastocysts to assess viability does not appear to be necessary and immediate embryo transfer after warming seems to have no negative impact on blastocyst implantation potential.
Chloé Fortin, Marc-André Sirard
Centre de Recherche en Reproduction, développement et santé intergénérationnelle (CRDSI), University Laval, QC
Nearly 65 % of ART cycles using fresh oocytes fail to produce a pregnancy. Ovarian stimulation prior to IVF influences ovarian environment and therefore oocyte quality. We believe that if a stimulation protocol fails to generate embryos having the potential to induce pregnancy, it could be related to abnormal follicular conditions. Moreover, RNA analysis of the granulosa aspirated with the oocyte could be used to identify the general degree of follicular differentiation and to make proper modification at the next cycle.
Materials and methods
Microarrays were used to analyze the gene expression in granulosa cells of IVF patients (n=32) according to the outcome (non-pregnant vs pregnant). 21 genes were then selected for further qPCR analysis using granulosa cells of 160 IVF patients (REB approved U LAVAL).
Following the microarrays data analysis, more than 200 genes were found differently expressed between the two groups (fold change >1.5, P <0.05). These genes include UMODL1, a gene positively regulated by FSH and recently studied in mice for its possible role in accelerated follicle depletion and ovarian degeneration. CCL3 and CXCL8 are also examples of genes that were up-regulated in the non-pregnant group. CCL3 is a chemokine involved in recruitment and activation of neutrophils during acute inflammatory process. CXCL8 is another chemokine holding important ovarian functions. These are associated with luteinization of granulosa cells and regulation of steroid synthesis. PTMA, a gene protecting from apoptosis, was down-regulated in the negative group, showing that this process is also affected.
Analysis of gene expression related to negative IVF outcome has highlighted potential markers of faulty follicular conditions. qPCR analysis will be used to confirm that these genes may explain the follicular status associated with incompetent oocytes. These markers could indicate if a given cycle was characterized by over growth, over-luteinization, early or late trigger. Further optimization of the stimulation protocol according to the patient’s follicular response could improve success at the next stimulation cycle.
The granulosa cell samples were obtained from Montreal Fertility Centre, Procrea Québec, Ottawa Fertility Centre and Reproductive Care Centre in Toronto
Kim Garbedian1,2, Alexander Lagunov1,2, Nora Zwingerman3 , Tom Hannam1,2
1 Colorado Centre for Reproductive Medicine (CCRM)- Toronto; 2 Hannam Fertility Centre, Toronto, ON; 3 University of Toronto; Toronto, ON
Introduction: DNA fragmentation index (DFI) is often used in addition to semen analysis to identify male factor infertility in couples. The impact of elevated DFI levels on IVF outcomes in the literature is inconclusive1. Therefore, this study examined the impact of elevated DFI levels on IVF success in patients undergoing Comprehensive Chromosome Screening (CCS).
Methods: DNA fragmentation index (DFI) was retrospectively evaluated in a cohort of 103 couples, 40 with CCS, undergoing IVF at a private fertility center in Toronto. IVF cycles between January 2015 and April 2016 were included. Women >38 years with AMH
Results: Of the included couples, 71.8% (n=74) had a normal and 28.2% (n=29) had an elevated DFI. There was no significant difference in female demographics (age, gravida, AMH, and BMI) or IVF cycle parameters (number of oocytes, number of fertilized embryos, blastocyst conversion, and number of cryopreserved embryos). In the overall cohort, a significant difference in clinical pregnancy rate was not seen in couples with normal vs. elevated DFI (62.7% vs. 58.3%, P=0.710). In the CCS sub-group (n=40), there was a trend towards higher clinical pregnancy (70.8% vs. 50.0%, P=0.574) and lower euploid implantation rate (64.6% vs. 37.5%, P=0.357) in the normal (n=33) vs. elevated DFI (n=7) group. No significant difference in the ploidy ratio was seen.
Conclusion: Despite optimized embryo selection through CCS, a trend towards lower clinical pregnancy and euploid implantation was seen in couples with an elevated DFI. However, it was reassuring that elevated DFI did not impact ploidy rate. Further data collection will be necessary to investigate this novel and interesting relationship.
- Zhan, Z et al., J Assist Reprod Genet. 2015. 32(1): 17-26.
Ashley Gilman, Grace Younes, Samer Tannus, WeonYoung Son, Peter Chan, William Buckett
MUHC Reproductive Centre, Montreal, QC
Nowadays, Canadian couples are often seeking fertility treatment at an older age. This can lead to poor-response during ovarian stimulation and fewer oocytes at OPU.
Another challenging population to treat are male patients with azoospermia and abnormal semen parameters including impaired sperm chromatin integrity. Advances in ICSI and surgical sperm retrieval have improved outcomes for this population.
Couples with both of these challenging male and female factor infertility causes pose a unique challenge.
Materials and Methods
This descriptive retrospective cohort study examined all ‘poor-responder’ patients (defined as ≤3 oocytes retrieved at OPU) undergoing an IVF cycle at the MUHC Reproductive Centre using surgically retrieved sperm between January 1 2009 and December 31 2015. All cycles meeting these criteria were included.
79 patients met these criteria. The mean age of the female patients was 38.3 years (SD=4.4). The implantation rate was 16.6%. The clinical pregnancy rate (CPR) was 11.3% and live birth rate (LBR) was 6.0%.
No embryo transfer (ET) took place in 34.7% of patients. Reasons for no ET were: no fertilization (55.0%), poor embryo quality (17.5%), no sperm found after surgical sperm retrieval (7.5%) and no MII (20.0%).
The majority of male patients underwent TESA (63.5%), followed by microTESE (20.0%). The remainder had TESE, PESA and MESA (6.1%, 6.1% and 4.3% respectively).
Compared with other poor responders during the same period, outcomes are similar. 1235 cycles were performed using ejaculate and ICSI or 50/50 IVF/ICSI for ‘poor-responder’ patients. Mean female age was 38.9 years (SD=3.6 years), implantation rate was 11.1% (P=0.14), CPR was 9.3% (P=0.50) and LBR was 5.8% (P=0.87).
This study represents the largest Canadian cohort of ‘poor-responder’ patients with surgical sperm retrieval. Patients with OA and NOA require surgical sperm retrieval for fertilization, and this study does not show any significant difference compared to other female-factor poor responder patients using ejaculated sperm. Further study in the use of testicular sperm poor responders with repeated failure is needed. In the meantime, appropriate counselling about realistic success rates is warranted.
Alyse Goldberg1, Shoba Sujana Kumar1, Ellen Greenblatt2
1University of Toronto, Division of Endocrinology and Metabolism, Women’s College Hospital, 2University of
Toronto, ON; Division of Reproductive Sciences, Mount Sinai Hospital, Toronto, ON
There is ongoing debate regarding initiating levothyroxine (LT4) therapy prior to conception in patients with subclinical hypothyroidism (SCH) (specifically, TSH> 2.5-4mIU/L, normal free thyroid hormones), particularly prior to assisted reproductive treatment (ART) outcomes. Congruent with recent guideline changes, our centre raised the threshold of initiating LT4 prior to ART from >2.5 mIU/L to TSH >4mIU/L. Obstetrical benefits of maternal TSH
Methods: A retrospective chart review was completed on women attending our fertility centre who achieved pregnancy (positive bHCG on luteal day (LD) 14) between November 1st, 2014 and December 1st, 2015. We included all women with a recorded TSH prior to their fertility cycle (TSH1) and on LD 16 (TSH2). Women who had a TSH1<0.3, or >4mIU/L were excluded, as well as women on LT4 at baseline who had a TSH1 >2.5mIU/L. Using logistic regression analyses, we compared the likelihood of clinical pregnancy rates (CPR) among three groups: baseline TSH<2.5, baseline TSH 2.5-4 and those on LT4 at baseline with a TSH<2.5.
Results: We had 482 women who met inclusion criteria. Mean age was 34.9 (+/- 4.2) and did not differ between the 3 groups. There were 333 women with a TSH12.5 as compared to those with a TSH22.5 mIU/L as compared to those with a TSH2
Conclusions: We have found that clinical pregnancy outcomes are equivalent between women with an early pregnancy TSH 2.5mIU/L. Our findings support recent guidelines that recommend against empirically initiating LT4 prior to pregnancy in women with a mildly elevated TSH.
Further studies are warranted to confirm that no difference in live birth rates are observed in association with mild elevation in TSH in early pregnancy.
Hala Gomaa, Rania Baydoun, Samuel Soliman
New Life Fertility Centre, Mississauga, ON
Introduction: Calcium Ionophore A23187 is highly selective for Ca2+; it is commonly used to increase intracellular Ca2+ levels in intact cells. Many studies showed it can be an effective treatment to improve fertilization rate, embryo development and pregnancy outcome. The aim of this study is to evaluate the impact of using Ca2+ Ionophore in IVF/ ICSI on embryonic development and pregnancy outcome in patients with poor embryo development in previous cycles.
Method: This is a retrospective study conducted at the private New Life Fertility clinic. We have identified and reviewed health record of 44 patients underwent repeated IVF/ ICSI cycles, first cycle without use of Ca2+ ionophore and the following cycles in which Ca2+ ionophore was used . We analyzed clinical data, including demographic information, medical history, ovarian stimulation protocol and ART outcome. The primary outcome measures were the number of mature oocytes, fertilization rate and number of good quality embryos. The secondary outcome is pregnancy rate and viable ongoing pregnancy.
Results: A total of 44 patients underwent 91 IVF/ICSI cycles. We compared the results of the cycles with use of Ca2+ ionophore [47 cycles] to the outcome of the previous IVF cycles for the same patients without Ca2+ ionophore [44 cycles]. Our results show that there is non- significant difference in fertilization rate [80.3% vs 83.5%], blastocyct rate [56% vs 46.5%] or number of good quality embryos > 3AA [18% vs 27%]. When cumulative pregnancy rate was compared, non-significant differences was observed (60% vs 43.7%) (P=0.12) and slightly higher on going pregnancy rate was observed in Ca2+ ionophore cycles (50% vs 27%) (P= 0.053).
Conclusion: Our data shows that using Ca2+ ionophore can improve blastocyst rate and may improve ongoing pregnancy rate but no significant impact on fertilization rate or good quality embryo number.
Keywords: Ca2+ ionophore, ICSI, fertilization rate, embryo development, pregnancy outcome.
Kelly Gray1, 2, Gerry Courtney1, Gary Nakhuda1, 2
1Olive Fertility Centre, Vancouver, BC; 2University of British Columbia, Vancouver, BC
Objective: To understand the role of the nurse in integrating a comprehensive chromosomal screening (CCS) program into the IVF clinic.
Background: CCS cycles present increased complexity compared to the ART cycle and require significant consideration for patient preparation, teaching, and counselling. CCS also requires increased coordination and collaboration between multiple departments within the clinic. The role of the IVF nurse has been documented to be integral in these aspects of patient care in the fertility clinic1. In order to understand and qualify the nurse’s role specific to CCS a review of nursing practice was undertaken at a Canadian fertility centre that has integrated a large, robust CCS program.
Materials & Methods: The nurse’s role in a CCS cycle was reviewed for components, flow and time required. Challenges and opportunities for the nursing team were identified. This program evaluation project involved observation, department meetings and individual interviews with nursing staff.
Results: The nursing staff volunteered their experiences of integrating a CCS program into their current practice. The nurse’s roles and responsibilities were outlined and recorded. Analysis of interviews and surveys identified the following themes: an increase in nursing time is required for patient teaching and counselling; the need for additional education for nurses specific to CCS; a recognition of the increased complexity of both coordinating the CCS cycle and the decision making process for patients. Challenges identified: counselling and supporting patients when learning of negative results which were felt to be more complex than standard IVF. Opportunities identified: the addition of an onsite medical genetics counsellor to the team; increased collaboration and open communication between all departments.
Conclusion: The expansion of a fertility clinic’s program to include CCS has significant implications for nursing practice and the role of the IVF nurse coordinator. Nurses felt that both additional time and training were required to successfully implement CCS into their current practice as well as the need for ongoing nursing support of patients throughout the process. Areas for future study include exploring both the patient experience of undergoing a CCS cycle and how nurses can best support them particularly when discussing negative results.
Support: no financial support was received for this project.
- Applegarth, Judith, Dwyer, Trudy, Moxham, Lorna, & Happell, Brenda. (2013). Identifying and acquiring the contextual skills and knowledge for nursing practice in assisted reproductive technology: a grounded theory study. Journal of Clinical Nursing, 22(11-12), 1738-1747. doi: 10.1111/j.13652702.2012.04275.x
Kelly Gray1,2 , Beth Taylor1,2
1Olive Fertility Centre, Vancouver, BC; 2University of British Columbia, Vancouver, BC
Objective: To describe the use of social media (SM) amongst the IVF clinics in Canada
Background: SM has taken on a life of its own with Facebook boasting over a billion users and sites such as Twitter and Instagram growing daily1. Canadians lead the world in number of internet page views, second only to the United States in number of hours spent online, and are leaders in SM use with over 19 million Facebook users1. SM is also being used for gathering health information2 and by providers and clinics to not only engage and educate patients but also to promote themselves3. While there is some work to look at this phenomenon in the US3 the Canadian context has not been explored. An examination of the current SM and online presence of Canadian IVF clinics is therefore warranted.
Materials and methods: The social media presence of 36 Canadian IVF clinics was examined. Fertility clinics were identified through CFAS.ca. Websites were identified either through CFAS.ca or a google search. Twitter and Facebook were then cross-referenced and individual clinic sites and accounts identified. Facebook sites were evaluated for activity, content, and number of Likes. Twitter accounts were evaluated for activity and Followers. Clinic websites were also evaluated for active links to social media, and the inclusion of a clinic and whether the blog allowed for social media sharing.
- 94% (n=34) have websites or a webpage
- 67% (n=24) have a Facebook account/site
- 47% (n=17) have twitter account
- 70% of these have active links on their clinic website Facebook and/or Twitter
- 5% (n=11) have a blog , only 3 have the ability for users to share a blog post to social media directly.
- Regional differences noted in social media use; larger urban centres with multiple fertility clinic more frequently used social media (BC, ON)
- Differences noted by type of clinic; Hospital based clinics and satellite clinics less likely to use social media
Conclusion: Canadian fertility clinics have largely adopted an online presence most commonly through a website. Many though have not leveraged SM and opportunities to increase a clinic’s online presence through SM have been missed ie. Active SM links; ability for users to share directly from the website/blog. Regional and environmental differences in social media use were noted, suggesting that social media may be being leveraged for marketing purposes in more competitive markets. While SM is effective at promotion it is also important for patient engagement and education4. Future research is warranted to explore IVF patients’ use and engagement with social media, care providers comfort with social media platform and the efficacy of social media as a tool to engage patients and promote one’s practice in the Canadian context.
- Canadian Internet Registration Authority (CIRA), 2015
- Oh, H. J., Lauckner, C., Boehmer, J., Fewins-Bliss, R., & Li, K. (2013). Facebooking for health: An examination into the solicitation and effects of health-related social support on social networking sites. Computers in Human Behavior, 29(5), 2072-2080. doi: http://dx.doi.org/10.1016/j.chb.2013.04.017
- Omurtag, K., Jimenez, P. T., Ratts, V., Odem, R., & Cooper, A. R. (2012). The ART of social networking: how SART member clinics are connecting with patients online. Fertility and Sterility, 97(1), 88-94. doi: http://dx.doi.org/10.1016/j.fertnstert.2011.10.001
- Royal College of Physicians and Surgeons of Canada. “Is your practice social media savvy? Four tips to get you started!,” Dialogue, (January 2014) Vol. 14, No.1.
Joanna Greer1, Leila Maghen1, Michael Crowe1, Paul Bingil1, Thomas G. Hannam2, William B. Schoolcraft3,
Alexander Lagunov1, Jason E. Swain4
1CCRM Toronto, Toronto, ON; 2Hannam Fertility Centre, Toronto, ON; 3Colorado Centre for Reproductive Medicine, Lone Tree, CO; 4CCRM IVF Network, Lone Tree, CO
Introduction: Macromolecule supplementation of culture media for human embryos is an important consideration of optimizing the culture systems and laboratory outcomes. Protein used in most media serves multiple purposes including membrane stabilization. Thus, protein concentration may be an important consideration during procedures that disturb or disrupt the cell membrane, such as denuding and ICSI.
Methods: A prospective randomized trial using sibling oocyte splits to examine impact of increased protein concentration during denuding and ICSI. All oocytes were placed into Quinn’s Advantage Cleavage Media (CM) containing 10% SPS (Sage) following retrieval for 3-4hrs incubation until denuding. Prior to denuding, sibling oocytes were split 50/50 into the control and test groups. The control oocytes were denuded using Cumulase (Origio), and CM containing 10% SPS. ICSI injection took place in CM with 10% SPS. Test oocytes were treated in an identical manner using CM containing 20% SPS for denuding and injection. All injected oocytes were cultured in CM containing 10% SPS following injection a 5% CO2, 5% O2 incubator. Fertilization was assessed ~18 hours following injection, with blastocyst development assessed on Day 5 and Day 6. Data were analyzed using Student’s t-test, p<0.05.
Results: Embryos from 11 patients were assessed (Control= 79, Test= 65 ). The mean patient age was 36.1 ± 3.45 years.
|Fertilization Rate (2PN)||Day 1 Lyse rate||Day 5 Usable Blastocyst Rate||Day 5/6 Usable Blastocyst Rate||Total Blast Conversion Rate|
|Control (10% SPS)||74.4%||6.9%||11.8%||41.2%||58.8%|
|Test (20% SPS )||90.8%||0.0%||20.0%||34.3%||45.7%|
Conclusions: These data suggest that 20% SPS may be superior to 10% SPS when used for ICSI in improving fertilization and reducing lysing rates, though no statistical significance was reached.
Vanessa Gruben1, Francoise Baylis2
1University of Ottawa, Ottawa, ON; 2Dalhousie University, Halifax, NS
Canadians engaged in a reproductive project, who are searching the internet for third-party gametes, will likely stumble across price lists for human sperm and eggs, and may notice that, unlike sperm, eggs are subject to the goods and services tax (GST). This raises a number of legal and ethical questions, which this paper seeks to address. First, it considers whether Canada’s laws governing the purchase of sperm and eggs are inconsistent: for ethical reasons, the Assisted Human Reproduction Act prohibits the purchase of human sperm and eggs in Canada, yet the Excise Tax Act defines sperm and eggs as “taxable supplies” that are subject to the GST. Second, this paper explores the possible reasons why the tax rate for sperm is 0% while the rate for eggs is between 5 and 15%. Finally, this paper examines the (potentially unintended) result of these legal provisions on the Canada Revenue Agency, which is required to collect taxes on illegal transactions involving the sale and importation of human eggs and to penalize those who fail to pay taxes on these illegal transactions.
Paul Grunberg1,2, Peter Chan1,3,4 Kirk Lo1,3, Janet Takefman1, Neal Mahutte5, Sophia Ouhilal5, Phyllis
1McGill University, Montreal, QC; 2Jewish General Hospital and the Lady Davis Institute, Montreal, QC; 3McGill
University Health Centre; 4Mount Sinai Hospital, Toronto, ON; 5Montreal Fertility Centre, Montreal, QC
Introduction: Diagnosis and treatment of infertility engenders psychological distress. Patients may have different needs for information and support during treatment, depending on gender and cultural background. The current study examined concerns associated with infertility in a large and diverse sample of men and women seeking fertility treatment.
Materials and Methods: Participants were recruited from fertility clinics in Montreal and Toronto. They completed an anonymous survey online that assessed experiences during assessment and treatment. The following concerns related to infertility and its treatment were rated from 0 (no concern) to 5 (very concerned): decision-making, exposing the body during medical examinations, sex life, relationships with partner and with family/friends, desire to have child, not becoming parent, gender identity.
A sample of 236 men and 283 women were included in the present study. Mean age was 36.54 years (SD = 5.51). Approximately half of the sample were immigrants (n = 274, 52.8%) who had lived in Canada for an average of 10.76 years (SD = 9.67). Most participants had no children (71.9%) and median duration of treatment was six months to one year. The most common treatment reported was IVF (44.5%).
Results: In the sample as a whole, independent samples t-tests found no differences in mean ratings for concerns between men and women. This held true for the immigrant group. However, among those born in Canada, women reported greater concern for sex life (P = .044) and desire to have a child (P = .047) than did men. Compared to those born in Canada, immigrants reported greater concern regarding decision-making (P < .001), exposing the body in medical examinations (P < .001), sex life (P = .002), family/friend relationships (P = .001), partner relationship (P < .001), and desire to have a child (P < .001). Immigrant women reported greater concern about the impact of infertility on their female identity (P = .005) than women born in Canada.
Conclusions: Gender and immigrant status were related to concerns associated with the diagnosis and treatment of infertility. Infertility patients may benefit from patient-centred interventions that acknowledge individual needs for information and support.
Kirah Hahn1, Sergey I. Moskovtsev1,2, Ari Baratz1,2,3, Karen Glass1,2,3, Prati Sharma1,2,3, Clifford Librach1,2,3
1CReATe Fertility Centre; 2Department of Obstetrics and Gynecology, University of Toronto; 3Department of Gynecology, Women’s College Hospital, Toronto, ON
Introduction: Effective management of patients with few or rare spermatozoa represents an important challenge in the field of ART. This study reports on our experience in managing patients with suspected azoospermia and severe oligozoospermia through our micro-TESE Avoidance Program (MAP), a key strategy in the way our clinic helps patients secure spermatozoa on the day of IVF or ICSI and possibly avoid testicular surgery.
Materials & Methods: CReATe’s Andrology Laboratory Database was interrogated to generate a list of all attempts to cryopreserve semen samples between January 2010 and March 2016. Entries were then parsed by sperm count and patients were classified with either suspected azoospermia or severe oligozoospermia (count < 1 M/ml). The following data were extracted: number of visits per patient, number of samples suitable for freezing, and freezing method.
Results: Since January 2010, a cohort of 103 men with suspected azoospermia and severe oligozoospermia attempted to freeze their sample, representing 9% of all sperm freezing patients. A total of 288 semen deposits were made, of which 70% were classified as suspected azoospermic and 30% as severely oligozoospermic. Suitability for freezing was determined by the presence of motile or viable sperm; 53% of all suspected azoospermic samples and 6% of all oligozoospermic samples were deemed unsuitable for freezing. The majority (53%) of patients visited once, 17% came twice, 13% three times, and 17% provided samples over four times. Most samples were cryopreserved by a standard slow liquid nitrogen vapour protocol (91%) and 9% by vitrification, a method introduced in 2015. Since 2010, MAP patient involvement has averaged at 1.6 patients per month, with 1.5 deposits per patient in 2010 compared to 3.8 in 2015.
Discussion: Individuals with suspected azoospermia and severe oligozoospermia represent a small but striking proportion of patients enrolled in CReATe’s sperm freezing program. The variable likelihood of sperm freezing demonstrates the value of repeated banking, particularly for patients with suspected azoospermia or inconsistent sperm counts. While most samples were cryopreserved by slow vapour freezing, there has been a growing use of vitrification based on our recent publication. Given these results, we anticipate that repeated trials of sperm vitrification will emerge as the favoured strategy in the management of patients with few or rare spermatozoa.
Maria E. Haikalis, Jocelyn M. Wessels, Nicholas A. Leyland, Warren G. Foster
McMaster University, Hamilton, ON
Introduction: Endometriosis is an estrogen-dependent disease characterized by the growth of endometrial tissue outside of the uterus. Currently endometriosis can only be definitively diagnosed by laparoscopic surgery. On average diagnosis can be delayed by up to 12 years, hence alternative non-invasive methods are needed. microRNAs (miRNAs) are short non-coding RNA transcripts that post-transcriptionally regulate the degradation of genes, and has been implicated as a clinical marker of several diseases including endometriosis. However, miRNA expression patterns in women with endometriosis vs. controls are inconsistent in the literature, potentially the result of methodological differences and the failure to account for biological differences among endometriotic lesion types. We therefore hypothesize that restricting comparisons of miRNA expression exclusively to endometriotic lesions of the same type will clarify the literature.
Methods: We used qPCR to analyze the miRNA expression of miR-9, miR-21 and miR-424, miRNA species previously documented in the endometriosis literature, in 8 ectopic (n=8), matched-eutopic (n=8) and control (n=7) samples. All of the ectopic samples were histopathologically-confirmed ovarian endometriomas. Each gene was compared to two reference genes SNORD95 and SNORD96A which we showed were stably expressed. One-way ANOVA analyses were performed for each target gene, as well as paired t-tests between the three test groups. A Kruskal-Wallis analysis of ranks test and Mann-Whitney U test were performed when appropriate.
Results: Preliminary analyses revealed that, compared to controls, endometriomas and eutopic samples showed a non-significant trend towards an increase in miR-9 expression (P= 0.358 and 0.375, respectively). Compared to controls, the miR-21 expression in endometriomas and eutopic samples showed no significant changes (P= 0.646 and 0.772, respectively). Finally, miR-424 expression in ectopic endometrium was not changed, but a non-significant trend towards an increase was observed in eutopic samples compared to controls (P= 0.841 and 0.727, respectively).
Conclusions: Our results suggest that these previously identified miRNAs are not suitable clinical markers of endometriosis. We propose that next-generation sequencing and extending our analysis to include peritoneal and deep-infiltrating lesions will identify novel markers of endometriosis.
Robert Hemmings1,2, Bander Kutbi1, Simon Phillips1
1Ovo Fertility clinic, Montreal, QC; 2McGill University, Montreal, QC
Objectives: Macklom and Brosens (2014) suggested that human endometrium responds differently when exposed to good quality embryos and poor quality embryos in term of gene activation. Therefore when two embryos are transferred (DET), the addition of a poorer quality embryo might decrease the chances of pregnancy of a good quality embryo. The objective of this study was to assess the validity of this hypothesis in a clinical setting.
Material and methods: In order to establish if there was any negative impact of transferring a poorer quality embryo with a high quality embryo (HQE), we analysed the results of DET retrospectively for cycles performed in 2008 and 2009 at the ovo fertility clinic. This period was selected since it was prior to the Quebec government IVF coverage which promoted eSET and discouraged DET.
In order to validate the results of two HQE, we also analysed the results from cycles with eSET during this time period where two HQE could have been transferred as demonstrated by the vitrification of at least one other HQE.
Three groups of patients were therefore compared:
Group 1: 64 patients who underwent DET with two good quality embryos.
Group 2: 77 patients who underwent DET with one good quality and one poor\average quality embryo.
Group 3: 16 good prognosis (with more than one embryo to transfer) patients who underwent single embryo transfer (SET)
Pregnancy rates (PR) and multiple pregnancy rate (MPR) were compared by Chi-Square.
|Clinical Pregnancy rate||Multiple pregnancy rate|
|Group 1||65% a||41% d|
|Group 2||58% b||33% e|
|Group 3||50% c||0%|
a vs. b, p=0.38
d vs. e, p=0.32
Conclusions: This study suggests that the simultaneous transfer of a HQE along with a poorer quality embryo does not decrease the chances of implantation of the HQE. Although the difference is not significant there is a clinically interesting difference in the multiple pregnancy rate between the two groups where two embryos were transferred. Further suggesting that the HQE implants independently of the presence or otherwise of another embryo.
This study is limited by the retrospective nature of the analysis and the total number of cases that could be included.
Macklon NS and Brosens JJ. 2014. The human endometrium as a sensor of embryo quality. Biol Reprod. 91(4):98
Philip J. Uren1, La-Toya Williamson1, Andrew D. Smith2, Douglas T. Carrell3, Haig Karsian1, Alexander Lagunov4, Leila Maghen4, Jason Swain4, Tom Hannam5, Alan Horsager1,2
1Episona, Inc., Pasadena, CA; 2University of Southern California, Los Angeles, CA; 3University of Utah, Salt Lake City, UT; 4Fertility Lab Sciences, LLC, Toronto, ON; 5Hannam Fertility Centre, Toronto, ON
Introduction: In 2015, Episona and their academic partners at the University of Southern California and University of Utah published a retrospective study investigating epigenetic differences in sperm samples from both known-fertile donors, and men in couples undergoing fertility treatment with female factors ruled out. It was demonstrated that distinct epigenetic differences existed between these two populations and that unknown samples could be diagnosed as likely to have male-factor fertility problems based on these patterns. These findings have formed the basis of an entirely novel, epigenetic-based diagnostic test for male infertility developed by Episona, called Seed.
Materials & Methods: To establish Seed as a diagnostic test with significant clinical utility requires validation in a prospective clinical population. We have partnered with 11 major fertility clinics in Canada and the United States to enroll several hundred patients from a wide-range of geographical locations. A small subset of these patients were used to further optimize our predictive algorithms. The remainder of the patients were used for prospective validation that Seed could be used to predict fertility status in male patients.
Results: We will report on our follow-up prospective validation study. We establish that our diagnostic models, trained using data from our earlier study, retain high sensitivity and specificity on this more diverse, prospective dataset. Further, we will show that shipping semen samples at ambient temperature for subsequent epigenetic analysis is viable. We will also present our findings on the relation between sperm epigenetic marks and a wide range of health and well-being data collected from study participants. Finally, in addition to validating our models on Illumina’s 450K Human Methylation array, we will describe validation using a different epigenetic profiling technology: whole-genome bisulfite sequencing.
Conclusions: In contrast to the array of diagnostic tests run on female partners, the male routinely only undergoes a semen analysis. While this can uncover gross problems such as azoospermia, it is insensitive, and many couples receive the unsatisfactory ‘diagnosis’ of unexplained infertility. Thus, an epigenetic-based diagnostic test could provide significant insight into the root causes of male infertility and guidance into how best to treat the infertile couple.
1The Create Fertility Centre, Toronto, ON; 2Department of Obstetrics and Gynecology; 3Department of Physiology; 4Institute of Medical Sciences, University of Toronto; 5Department of Gynecology, Women’s College Hospital, Toronto, ON; 6Toronto General Research Institute (TGRI), University Health Network (UHN), Toronto, ON
Introduction: We previously demonstrated that Mesenchymal stromal cells (MSCs) derived from first trimester human umbilical cord (FTM-HUCPVCs) are a promising allogeneic cell candidate for regenerative medicine. Like MSC from other sources, they are typically expanded using fetal bovine serum (FBS). Production of MSCs for clinical use requires xeno-free cell culture conditions. Human Platelet Lysate (HPL) is a cytokine rich replacement for FBS and used in clinical practice. We aimed to compare phenotypic, homing and angiogenic profiles of FTM-HUCPVCs expanded in FBS vs. HPL.
Methods: FTM-HUCPVCs expanded in either 10% FBS or 5% HPL were immunophenotyped using flow cytometry for MSC-, pericyte and endothelial cell-associated markers. An in vitro aortic ring assay adapted to study angiogenesis, was utilized to analyze homing and integration of co-cultured FTM-HUCPVCs (day1) and effects on endothelial network development (day4). This was followed by gene expression profiling using a growth Factor PCR Array. In addition, we performed an in vivo Matrigel™ plug assay where 5.0 x105 MSCs suspended in Matrigel™ were injected subcutaneously into 11-week-old nude mice. Plugs were isolated after two weeks and microvasculature formation was imaged.
Results: At passage 3 and 5, FTM-HUCPVCs in either FBS and HPL were 99% and 98% double positive for pericyte- and MSC markers CD146 and CD90, and 66% and 57% positive for SSEA4, a multilineage differentiation potential marker, respectively FTM-HUCPVCs homed to peripheral developing endothelial networks under both conditions and showed similar integration into, and expansion of, network loop formation. FTM-HUCPVCs (FBS and HPL) contributed to similar network growth (141±12 mm and 153±11 mm respectively; P=0.27), and significantly greater network growth compared to untreated networks (105±6mm; P=0.003). FTM-HUCPVCs, grown in both conditions expressed high levels of angiogenic factors such as VEGFA, C, FGF1, PDGFC and JAG1, in the aortic ring assay. Within Matrigel plugs embedded with FTM-HUCPVCs, grown in either FBS or HPL, there was development of numerous functional blood vessels, perfused by blood cells, compared to no functional vessel formation in cell free controls.
Conclusions: FTM-HUCPVCs expanded in HPL exhibit similar immunophenotypical profiles, homing and angiogenic potential, both in vitro and in vivo, when compared to expansion under standard FBS conditions. Our data provides a strong foundation for development of serum-free/xeno-free GMP-compatible conditions to expand FTM-HUCPVCs for regenerative medicine applications.