Oral Presentations Clinical I

Natalia Yasovich1, Melissa Filice1, Sergey Moskovstev1,2, Andrée Gauthier-Fisher1, Kirk Lo1,3, Clifford L. Librach1,2,3
1CReATe Fertility Centre, Toronto, ON; 2Departments of Obstetrics and Gynecology and Physiology, University of Toronto, ON; 3Department of Urology, Mount Sinai Hospital, Toronto, ON; 4Department of Gynecology, Women’s College Hospital, Toronto, ON

Introduction: Azoospermia, the absence of sperm in semen, affects approximately 15% of infertile men. Non-obstructive azoospermia (NOA) represents approximately 60% of azoospermia, mainly caused by testicular failure or arrest of spermatogenesis. Testicular spermatozoa retrieval has been the only option for men with NOA, with limited success rates. Moreover, recovery of spermatozoa from testicular tissue is time-consuming, highly variable and labor intensive. There is a need to develop more efficient methods for sperm retrieval from surgical tissue and also to identify and isolate rare ejaculated spermatozoa. The purpose of this project was to investigate the use of imaging flow cytometry to identify rare ejaculate and testicular spermatozoa, and assess their morphology and maturation in NOA patients.

Materials and Methods: With institutional Research Ethics Board approval and written informed consent, excess ejaculate (n=5) and testicular samples (n=2) were obtained from NOA patients. Samples were processed by centrifugation and an extensive search using a micromanipulator was performed under a phase contrast microscope. When no spermatozoa were found, working media and cell pellets were stained with propidium iodide (PI). Imaging flow cytometry was performed using Image-StreamTM and data was analyzed using the IDEAS software.  Sperm were visually identified using area vs. aspect ratio for gating, and confirmed using PI staining for ploidy assessment.

Results: Using Image StreamTM,spermatozoa were identified in all ejaculate samples, where no spermatozoa had been found using traditional techniques, ranging from 1 to 320 per whole ejaculate (mean88±131). In testicular samples, 3 spermatozoa and 64 were identified by Image-StreamTM when none were found after extensive dissection and searching. Images of sperm from these samples suggest immature morphology, indicated by the presence of large heads and short tails. The percentage of sperm within the total population of cells imaged by the cytometer represented less than 0.005%.

Conclusion: Imaging flow cytometry provides an efficient and more advanced option to identify the presence of rare sperm in patients with NOA. Further analysis of sperm from NOA patients is required to assess their viability and maturation, as well as to investigate the use of biomarkers to capture and isolate these rare sperm for potential use in assisted reproduction.

Karen Glass1,2, Karen Buzaglo3, Shu Foong4,5, Eileen McMahon2,6, Jeff Roberts7,8, Lorne Cooper9
1CReATe Fertility Centre, Toronto, ON; 2University of Toronto, Toronto, ON; 3Clinique OVO, Montreal, QC; 4Regional Fertility Program, Calgary, AB; 5University of Calgary, Calgary, AB; 6Mount Sinai Fertility, Toronto, ON; 7Pacifc Centre for Reproductive Medicine, Burnaby, BC; 8University of British Columbia,
Vancouver, BC;
9Cancer Knowledge Network, Toronto, ON

Introduction: The CFAS Fertility Preservation Special Interest Group recognized that there is a lack of metrics in Canada for oncofertility.  In order to help improve access to care, more data about current referral practices in Canada for young cancer patients is required. Together with Cancer Knowledge Network (CKN), we developed a database to track oncofertility referrals across Canada to determine who and where referrals are originating from and to monitor patients’ decision-making regarding the use of available technology.

Methods:  Every fertility clinic in Canada was contacted to participate.  A total of 28 clinics accepted.  Each clinic was given a unique URL to log into the confidential database housed on the CKN secure website.  The clinics are instructed to answer four questions for each oncofertility referral that they receive.  The four preliminary questions are:  Age, gender, type of cancer, and referring physician specialty.  All data is entered without any patient identifiers.  Twenty-eight days after the initial entry a follow up email is sent to the clinic.  The fifth and final question is: “What did the patient decide to do?”.  Patients who declined consultation despite referral are accounted for.

Results:  By April 2016, a total of 184 entries were completed from 10 clinics across Canada.   The average age was 29.7 years.  10 patients (5 female, 5 male) declined consultation.  118/184 (64%) referrals came from medical oncologists. 45/56 (80%) male patients cryopreserved sperm. 20/128 (16%) females froze embryos; 22/128 (17%) froze oocytes; 7/128 (5%) froze both; 12/128 (9%) received GnRHa (3 of these patients also froze oocytes or embryos); 42/128 (33%) declined treatment.  74/184 (40%) referrals were for breast cancer, 43/184 (23%) were lymphoma, 11/184 (6%) cervical, 11/184 (6%) testicular, 9/184 (5%) colorectal.

Conclusions: We are pleased with the initial 4-month participation.  Canadian oncofertility data for both genders is now available. Clinics with known oncofertility practices are participating.   We plan to personally contact all clinics that have not participated yet to discover if they have received any oncofertility consults.  This database is helping to bring together the specialties of oncology and fertility. Ultimately in Canada, we hope to ensure every young patient with a cancer diagnosis receives appropriate counselling about their reproductive future.

Sadikah Behbehani, William Buckett, Weon-Young Son, Joseph Hasson
McGill University, Montreal, QC

Introduction: It is currently unclear whether markers of ovarian reserve predict cycle success and pregnancy outcome in IVF once there is a blastocyst to transfer. We conducted a retrospective cohort study to compare clinical pregnancy rates of single blastocyst transfers in patients with baseline FSH >10 IU/L to age matched controls with baseline FSH

Material and Methods: Among 1250 fresh single blastocyst transfer cycles performed at our center between the years 2013-2015. 128 transfer cycles were in women with baseline FSH >10 IU/L. From the same cohort, age matched controls with baseline FSH of

Results: Baseline characteristics of BMI and smoking rates were comparable between the groups. The mean baseline FSH in the high FSH group was 13±4.2 IU/L and 7±1.5 IU/L in the low FSH group. Patients in the high FSH group required more days of stimulation and higher doses of gonadotropins (9.9±2.2 vs 9±1.67, P<0.01; 3556 ± 1723 IU vs 2774 ±1419 IU, P<0.01, respectively). Endometrial thickness prior to transfer was similar between the groups (9.9±2 vs 10.4±6 P=0.29). In patients who had high FSH, there were significantly less oocytes collected and less blastocysts available for transfer (6.41±3.9 vs 7.5±4, P=0.01; 2.34±1.67 vs 2.84±1.85, P=0.01, respectively). Clinical pregnancy rates (defined as the presence of fetal heart activity by ultrasound at 6-7 gestational weeks) were similar between the groups (32.8% vs 40.6%, p=0.13). There was also no difference in level of beta HCG drawn 11 days after the transfer.

Conclusion: In patients with markers of low ovarian reserve, such as high baseline FSH, who have an embryo transferred at a blastocyst stage, clinical pregnancy rates are similar to age matched controls with normal baseline FSH. This is despite lower numbers of collected oocytes and available blastocysts. Although the response to ovarian stimulation may be diminished, once a blastocyst is transferred, oocyte quality may not necessarily be compromised and these patients still have good quality embryos and pregnancy rates.

Tamas Gotz1,2, Claire Jones1,2
1University of Toronto – Toronto, ON; 2Mount Sinai Fertility- Mount Sinai Hospital- Toronto, ON

Introduction: On December 21st, 2015 the Ontario Ministry of Health and Long Term Care began funding one cycle of IVF for any Ontarian under the age of 43, to a maximum of 5000 cycles per year1, which is below expected demand. Each fertility clinic had to create its own criteria for the distribution of limited numbers of funded IVF cycles. The primary objective of this study was to determine how fertility clinics were prioritizing patients for funded IVF and to determine who was involved in setting the criteria for prioritization.

Methods: Fertility clinics providing IVF in Ontario were identified through the CFAS directory and an online search. An electronic survey was emailed to the Medical Director of each fertility clinic.

Results: From January to March 2016, twenty-five fertility centres providing IVF in Ontario were identified and sent our survey. We received 22 (88%) responses. All clinics reported providing access to funded IVF, and 100% already had a wait-list. There were 8 clinics that prioritized patients on a first-come first-served basis, 2 employed a lottery, 11 reported having multiple patient factors determine priority for funding, and 1 declined to answer. Of the clinics reporting multiple factors, the five most important factors were first-come first-served (90.9%), older aged patients (81.8%), patients who were close to losing their eligibility for funding (63.6%), duration of infertility (36.3%), and duration at current clinic (36.3%). Every clinic had created their prioritization policy with the input of physicians, nurses, embryologists, and clinic staff. Only 6 clinics had consulted an ethicist and none had consulted members of the public.

Conclusions: There is wide variation in how clinics are choosing to distribute limited numbers of funded IVF cycles. Some clinics have chosen to prioritize patients in a first-come first-served manner, while others have chosen to prioritize patients based upon multiple factors that would favour older patients. This is the first study looking at how the new fertility program has been implemented by individual clinics. This information is important for patients to understand their chances of receiving a funded IVF cycle, as their chances may vary depending on which clinic they choose to go to. This study provides the public and government insight into how this new program is functioning in its first few months.

1 https://news.ontario.ca/mohltc/en/2015/12/ontario-announces-50-clinics-offering-government-funded-fertility-treatments.html

Dylan Cutler1, Anthony P. Cheung1, 2
1University of British Columbia, Vancouver, BC; 2Grace Fertility Centre, Vancouver, BC

Methods: Women with PCOS (n=100) and normal ovulatory women (n=50) seeking fertility treatment were recruited at Grace Fertility Centre (respective mean age ± SEM: 31.8 ± 0.9 vs. 35.2 ± 0.9, and BMI: 29.5 ± 0.7 vs. 24.2 ± 0.9). The “Depression Anxiety Stress Scale” and “Fertility Quality of Life Tool” were used to assess psychological well-being. Additionally, demographic, clinical and laboratory data were recorded. Data were analysed using Student’s t-tests or Mann-Whitney tests while correlation was assessed using Spearman’s Rank tests.

Results: Women with PCOS had significantly higher anxiety than normal ovulating women (respective median scores ± SEM: 6.0 ± 0.7 vs. 2.0 ± 0.8, P = 0.002). Anxiety in women with PCOS was not associated with obesity or hirsutism. Women with PCOS had lower “mind-body” scores than controls, a sub-scale of the quality of life assessment (66.7 ± 2.8 vs. 77.1 ± 3.0) but differences were not statistically significant. No significant differences were found between levels of depression (3.0 ± 0.8 vs. 3.0 ± 0.7), stress (11.0 ± 0.9 vs. 9.0 ± 1.2), or overall quality of life (67.2 ± 2.1 vs. 67.2 ± 2.1).

Conclusion: Increased anxiety in women with PCOS compared to normal ovulating women suggests that PCOS carries additional emotional distress beyond an infertility diagnosis. This distress could not be explained by physical characteristics of PCOS. Contrary to previous research, no differences in stress, depression, or quality of life were found which may be due to both groups being affected by infertility or the use of different measurement tools. The relationship between PCOS and psychological factors requires further research to optimize management.

Pavan Gill
University of Toronto

Impact Statement: Immigrant women in Toronto approach fertility care differently, and this needs to be understood and addressed by healthcare providers.

Objective: To understand the experience immigrant women in Toronto have obtaining infertility treatment compared to Canadian born women.

Methods: All female patients in heterosexual relationships were invited to complete an anonymous survey in a university-affiliated hospital-based fertility clinic. Data were obtained on socio-demographic characteristics, infertility status and time to treatment. Statistical analysis, including chi-square and ANOVA regression was completed using JMP software.

Results: The response rate of the survey was 86.6%. Two hundred and sixty five women completed the survey, of which 124 (47%) were immigrants and 141(53%) were Canadian born.  New Canadians more commonly left questions unanswered.  For example, 35% decline to answer questions related to income and 28% did not know or refused to answer questions about the cause of their infertility. The average age and marital status was similar among the groups, however, Canadian born women had more education. Thirty one percent of recent immigrants reported being unemployed. With respect to medical care, there was no overall difference in time from trying to conceive until seeing a physician between groups. (immigrants vs Canadians 22 vs 27m average time or 22 or 24 m median time respectively). However the total duration of fertility was significantly longer.  In addition the immigrant group in Canada for more than five years had a 47m average duration of infertility. This was significantly different than the other group (p<.05).The median duration was 36 m vs24 m in new immigrants compared to Canadian born women.  The most commonly reported reasons for delaying fertility care were “not knowing there was a problem” and “treatments being too expensive”.  Approximately 90% in both groups reported having a delay. Recent immigrants were less likely to consider bank loans as an option to pay for services but were no more likely to rely on family. While the majority of participants across all groups relied on their family physician to provide information on fertility services, a greater percentage (17%) of recent immigrants in comparison to Canadian born participants (7%) utilized the Internet to obtain information. Immigrants were also more likely to consider treatment outside of Canada.

Conclusion: Immigrant women in Toronto address their fertility needs when they have fewer resources and less social stability in comparison to Canadian born women. They do access fertility services but health care providers may be difficult to assure their trust and understanding of their medical situation. This may be a barrier to education and potentially success. Developing resources on the Internet and increasing collaboration with family physicians are two strategies that may be particularly effective among immigrant women.