The Blastulation Rate Is Negatively Associated With Euploid Rate.

OBJECTIVES: To study the association between the blastulation rate, the presence of 1 pronucleus (1PN) zygotes, and the ploidy of the cohort of blastocysts. METHODS: A cross-sectional study using the existing databases of 2 university fertility centres in Canada. We included 345 cycles from 235 couples who underwent next-generation sequencing preimplantation genetic testing for the detection of aneuploidy in the study. RESULTS: A total of 1456 blastocysts were biopsied. In multivariate analysis, only female age and the number of 1PN/2PN embryos showed a negative association with euploid ratio. Surprisingly, when the analysis was limited to cycles with no delayed blastulation, the blastulation rate was also negatively associated with the euploid ratio. CONCLUSIONS: This study sheds some light on the stages of early embryo development. Further study on the mechanisms governing embryo development and the different cell cycle checkpoints in embryo development is warranted.

Optimal endometrial thickness in fresh and frozen-thaw in vitro fertilization cycles: an analysis of live birth rates from 96,000 autologous embryo transfers.

OBJECTIVE: To study the effect of increasing endometrial thickness on live birth rates in fresh and frozen-thaw embryo transfer (FET) cycles. DESIGN: Retrospective cohort study. SETTING: National data from Autologous in vitro fertilization (IVF) embryo transfer and FET cycles in Canada from the Canadian Assisted Reproductive Technology Registry Plus (CARTR Plus) database for records between January 2013 and December 2019. PATIENTS: Thirty-three Canadians clinics participated in voluntary reporting of IVF and pregnancy outcomes to the Canadian Assisted Reproductive Technology Registry Plus database, and a total of 43,383 fresh and 53,377 frozen transfers were included. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy, pregnancy loss, and live birth rates. RESULTS: In fresh IVF-embryo transfer cycles, increasing endometrial thickness is associated with significant increases in the mean number of oocytes retrieved, peak estradiol levels, number of usable embryos, clinical pregnancy rates, live birth rates, and mean term singleton birth weights, and a decrease in pregnancy loss rates. However, live birth rates plateau after 10-12 mm. In contrast, in FET cycles live birth rates plateau after the endometrium measures 7-10 mm. The improvement in live birth rates with increasing endometrial thickness was independent of patient age, timing of embryo transfer (e.g., cleavage stage vs. blastocyst stage), or the number of oocytes at retrieval. CONCLUSIONS: In cycles with a fresh embryo transfer, live birth rates increase significantly until an endometrial thickness of 10-12 mm, while in FET cycles live birth rates plateau after 7-10 mm. However, an endometrial thickness <6 mm was associated clearly with a dramatic reduction in live birth rates in fresh and frozen embryo transfer cycles.

Fertility patients' use and perceptions of online fertility educational material.

BACKGROUND: Online educational information is highly sought out by patients with infertility. This study aims to assess patient-reported usage and helpfulness of fertility educational material on a clinic website and social media accounts. METHODS: Educational material was created on common fertility topics in text and video format and posted on the clinic website and social media accounts. At the first consultation for infertility, patients were provided with a postcard directing them to material online. At the first follow-up appointment, patients were invited to fill out a survey assessing whether patients viewed the online educational material and if they found the information helpful. RESULTS: 98.4% (251/255) of patients completed the survey, of which 42.6% (106/249) looked at the online material. Of those who viewed the online information, 99.1% (115/116) found the information helpful or somewhat helpful and 67.6% (73/108) found reading the material online better prepared them for making fertility decisions at their doctor's appointment. CONCLUSION: Patients found online fertility information on the clinic website and social media accounts useful for making fertility treatment decisions. Providing online educational material has the potential to improve patient care by empowering patients with the knowledge to make more informed treatment decisions, and improving the quality of the time spent with the physician.

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

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

Management of thin endometrium in assisted reproduction: a clinical practice guideline from the Canadian Fertility and Andrology Society.

The impact and management of thin endometrium is a common challenge for patients undergoing assisted reproduction. The objective of this Canadian Fertility and Andrology Society (CFAS) guideline is to provide evidence-based recommendations using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) framework on the assessment, impact and management of thin endometrium in assisted reproduction. The effect of endometrial thickness on pregnancy and live birth outcomes in ovarian stimulation and IVF (fresh and frozen cycles) is addressed. In addition, recommendations on the use of adjuvants to improve endometrial thickness and pregnancy outcomes are provided.

Effect of endometrial injury on in vitro fertilization pregnancy rates: a randomized, multicentre study.

PURPOSE: To determine if endometrial injury prior to the first or second in vitro fertilization (IVF) cycle affects clinical pregnancy rates. METHODS: This study was a randomized, multicentre, controlled study performed at three Canadian outpatient fertility clinics. Patients undergoing their first or second IVF cycle were randomized to a single endometrial injury 5-10 days prior to the start of gonadotropins in an IVF cycle compared to no injury. The primary outcome was clinical pregnancy rate. Secondary outcomes were live birth rates, implantation rate, endometrial thickness, number of oocytes retrieved and the rate of embryo cryopreservation. RESULTS: Fifty-one women were randomized (25 in the en dometrial injury group and 26 in the control group); however, the study was terminated prematurely due to slow recruitment (target 332 patients). Groups were similar at baseline for: age, duration of infertility, BMI, day 3 FSH, and the number having first IVF cycle. The groups were similar for gonadotropin dose, endometrial thickness, number of oocytes retrieved, and embryo cryopreservation rate. The clinical pregnancy rate in the endometrial injury group was 52% (13/25) and 46% (12/26) in the control group (p = 0.45). Live birth rate in the endometrial injury group was 52% (13/25) and 35% (9/26) in the control group (p = 0.17). The implantation rate was also similar (58% vs. 45%, p = 0.17). CONCLUSIONS: This study did not detect a difference in implantation, clinical pregnancy or live birth rates; however, the lack of difference in this study may be because it was underpowered. CLINICAL TRIALS REGISTRATIONS: gov: NCT01983423.

No 346-Âge génésique avancé et fertilité.

OBJECTIFS: Sensibiliser la population à la baisse naturelle de la fertilité avec l'âge, chez les femmes et les hommes, et à l'égard de la reproduction naturelle et des technologies de procréation assistée (TPA); formuler des recommandations de prise en charge; et analyser les méthodes d'évaluation du vieillissement ovarien. OPTIONS: La présente directive clinique passe en revue les options offertes pour l'évaluation de la réserve ovarienne et pour le traitement de l'infertilité faisant appel aux TPA chez les femmes d'âge génésique avancé infertiles. ISSUES: Les issues mesurées sont les valeurs prédictives de l'évaluation de la réserve ovarienne et les taux de grossesse découlant de la fertilité naturelle et de la fertilité assistée. DONNéES: Nous avons examiné des études publiées récupérées au moyen de recherches dans PubMed, Medline, CINAHL et la Bibliothèque Cochrane en juin 2010 à l'aide de mots-clés appropriés (ovarian aging, ovarian reserve, advanced maternal age, advanced paternal age, et assisted reproductive technology). Nous n'avons tenu compte que des résultats provenant de revues systématiques, d'essais cliniques, randomisés ou non, et d'études observationnelles. Aucune restriction de date ou de langue n'a été employée. Les recherches ont été refaites régulièrement, et les résultats ont été incorporés à la directive clinique jusqu'en décembre 2010. VALEURS: La qualité des données a été évaluée au moyen des critères énoncés dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs. Les recommandations quant à la pratique ont été classées conformément à la méthode décrite dans ce rapport. AVANTAGES, DéSAVANTAGES ET COûTS: Les patientes et les fournisseurs de soins primaires et spécialisés seront mieux renseignés sur le vieillissement ovarien, la baisse de la fertilité naturelle liée à l'âge et les TPA.

No. 346-Advanced Reproductive Age and Fertility.

OBJECTIVE: To improve awareness of the natural age-related decline in female and male fertility with respect to natural fertility and assisted reproductive technologies (ART), provide recommendations for their management, and to review investigations in the assessment of ovarian aging. OPTIONS: This guideline reviews options for the assessment of ovarian reserve and fertility treatments using ART with women of advanced reproductive age presenting with infertility. OUTCOMES: The outcomes measured are the predictive value of ovarian reserve testing and pregnancy rates with natural and assisted fertility. EVIDENCE: Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in June 2010, using appropriate key words ("ovarian aging," "ovarian reserve," "advanced maternal age," "advanced paternal age," and "assisted reproductive technology"). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated into the guideline to December 2010. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report. BENEFITS, HARMS, AND COSTS: Primary and specialist health care providers and women will be better informed about ovarian aging and the age-related decline in natural fertility and about options for ART.

The effect of age, ethnicity, and level of education on fertility awareness and duration of infertility.

OBJECTIVE: An increasing number of Canadian women are delaying child-bearing, despite a decrease in fertility with age. A longer duration of infertility is associated with a significant decrease in live birth rate, reinforcing the need for prompt access to fertility treatment. This study aimed to assess the fertility awareness of women attending a fertility clinic to determine whether fertility awareness is a factor in accessing treatment. METHODS: A quantitative cross-sectional survey evaluated fertility awareness and collected information about ethnicity, education level, and the duration of infertility for new patients. Fertility awareness was evaluated with questions about prevalence, causes, and treatment of infertility. RESULTS: The mean age of participants in the study was 34 years (range 23 to 44; n = 140). The duration of infertility before new patients first sought medical advice for infertility was less than one year in 52.9%, one to two years in 28.6%, two to three years in 12.9%, and four or more years in 5.0% of study participants. Fertility awareness was calculated as the percentage of correct responses to the survey questions. The mean fertility awareness for all study participants was 49.9% and this ranged from the lowest score of 9.1% to the highest score of 90.9% correct. Women waiting for longer than two years to seek medical help had lower fertility awareness (P = 0.038). In addition, fertility awareness was greater in women who had previously sought medical help for infertility from a family doctor, a gynaecologist, or another fertility clinic (P = 0.001). Higher fertility awareness correlated with a higher level of education (linear trend P < 0.001). Finally, fertility awareness also varied with ethnicity (ANOVA P = 0.025), but the age at which women of different ethnicities sought treatment was similar (ANOVA P = 0.13). CONCLUSION: Fertility awareness is associated with time to seek treatment, ethnicity, and level of education among new patients seeking medical treatment. This study demonstrates the need to educate women of reproductive age and identifies particular patient populations in Canada that would most benefit from further education about infertility.

Objectif : Un nombre croissant de Canadiennes reportent la grossesse, et ce, malgré la baisse de la fertilité qui est constatée avec l'âge. La prolongation de la durée de l'infertilité est associée à une baisse marquée du taux de naissance vivante, ce qui souligne la nécessité d'assurer un accès rapide au traitement contre l'infertilité. Cette étude cherchait à évaluer les connaissances en matière de fertilité chez des femmes consultant une clinique de fertilité, en vue de déterminer si de telles connaissances constituent un facteur pour ce qui est de l'accès au traitement. Méthodes : Une enquête transversale quantitative a évalué les connaissances en matière de fertilité chez de nouvelles patientes et a recueilli des données au sujet de leur ethnicité, de leur scolarité et de la durée de leur infertilité. Les connaissances en matière de fertilité ont été évaluées par l'intermédiaire de questions portant sur la prévalence, les causes et la prise en charge de l'infertilité. Résultats : L'âge moyen des participantes à l'étude était de 34 ans (plage : 23-44; n = 140). La durée de l'infertilité avant que ces nouvelles patientes aient pour la première fois cherché à obtenir l'avis d'un médecin à ce sujet était de moins d'un an chez 52,9 % d'entre elles; d'un à deux ans, chez 28,6 %; de deux à trois ans, chez 12,9 %; et de quatre ans ou plus, chez 5,0 %. Le pourcentage de bonnes réponses aux questions de l'enquête a été utilisé pour définir les connaissances en matière de fertilité. Pour l'ensemble des participantes à l'étude, le score moyen pour ce qui est des connaissances en matière de fertilité était de 49,9 % (plage : de 9,1 % à 90,9 %). Les femmes qui avaient attendu pendant plus de deux ans avant de chercher à obtenir l'aide d'un médecin comptaient des connaissances moindres en matière de fertilité (P = 0,038). De plus, les connaissances en matière de fertilité étaient supérieures chez les femmes qui avaient déjà cherché à obtenir de l'aide pour contrer leur infertilité auprès d'un médecin de famille, d'un gynécologue ou d'une autre clinique de fertilité (P = 0,001). Le fait de détenir des connaissances élevées en matière de fertilité était en corrélation avec une scolarité accrue (tendance linéaire P < 0,001). Enfin, les connaissances en matière de fertilité ont également varié en fonction de l'ethnicité (ANOVA P = 0,025); toutefois, l'âge auquel les femmes de différentes ethnicités ont cherché à obtenir un traitement était semblable (ANOVA P = 0,13). Conclusion : Chez de nouvelles patientes cherchant à obtenir un traitement médical, les connaissances en matière de fertilité ont été associées avec le délai avant la mise en œuvre de la démarche visant l'obtention d'un traitement, l'ethnicité et le niveau de scolarité. Cette étude démontre la nécessité de renseigner les femmes en âge de procréer et identifie les populations particulières de patientes canadiennes qui tireraient le plus profit d'une sensibilisation accrue au sujet de l'infertilité.

Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization.

BACKGROUND: Recent studies suggest that vitamin D may play a role in human reproduction. Our goal was to investigate whether vitamin D levels are predictive of implantation and clinical pregnancy rates in infertile women following in vitro fertilization (IVF). METHODS: We prospectively evaluated vitamin D status, as determined by serum 25-hydroxy-vitamin D (25[OH]D) levels, in a cohort of 173 women undergoing IVF at Mount Sinai Hospital, Toronto, Ontario. Serum 25(OH)D samples were collected within 1 week before oocyte retrieval. We classified patients as having sufficient (≥ 75 nmol/L) or insufficient (or deficient; hereafter referred to as "insufficient"; < 75 nmol/L) serum levels of 25(OH)D. We compared patient demographics and IVF cycle parameters between groups. The primary outcome measure was clinical pregnancy (intrauterine sac visible on ultrasound performed 4-5 weeks after embryo transfer). RESULTS: Of the included women, 54.9% had insufficient 25(OH)D levels and 45.1% had sufficient levels. Women with sufficient levels had significantly higher rates of clinical pregnancy per IVF cycle started (52.5%) compared with women with insufficient levels (34.7%; p < 0.001). Implantation rates were also higher in the sufficient 25(OH)D group, but the results were not statistically significant. Multivariable logistic regression analysis (adjusted for age, body mass index and day 5 [v. day 3] embryo transfer) showed that serum 25(OH)D level may be a predictor of clinical pregnancy (adjusted odds ratio 1.01, 95% confidence interval 1.00-1.03). INTERPRETATION: Our findings suggest that women with sufficient levels of vitamin D are significantly more likely to achieve clinical pregnancy following IVF. Vitamin D supplementation could provide an easy and cost-effective way of improving pregnancy rates; this merits further investigation. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01348594.

Addressing oncofertility needs: views of female cancer patients in fertility preservation.

A total of 41 questionnaires were returned from 64 respondents who consented to receive a questionnaire through the mail. Almost all valued the opportunity to receive consultation to address their fertility concerns and discuss fertility preservation options. Psychological stress, time pressure, and costs were identified as main factors affecting respondents' decision to proceed with in-vitro fertilization to cryopreserve oocytes or embryos. About one third indicated that the discussion of fertility matters was initiated by themselves, their friends, and families rather than their health care providers. The findings have identified several major barriers encountered by female cancer patients when seeking fertility preservation services.

Oocyte cryopreservation in Canada: a survey of Canadian ART clinics.

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

A randomized controlled trial of NuvaRing versus combined oral contraceptive pills for pretreatment in in vitro fertilization cycles.

OBJECTIVE: To determine whether use of the NuvaRing (Merck) for pretreatment in IVF cycles would result in better cycle control and patient satisfaction versus a 30-µg oral contraceptive (OC) pill. DESIGN: A prospective randomized, controlled study. SETTING: An academic, hospital-based fertility clinic in Toronto, Canada. PATIENT(S): Patients 18-37 years old, undergoing their first IVF or IVF/intracytoplasmic sperm injection (ICSI) cycle. INTERVENTION(S): OC versus NuvaRing for IVF pre-treatment. MAIN OUTCOME MEASURE(S): Patient satisfaction, ovarian suppression, and IVF cycle outcomes. RESULT(S): Demographic data were similar in both groups. There were no significant differences in side effects between the NuvaRing and OC pill group with the exception of more breast discomfort in the OC pill group. There were no differences in the protocols, days of stimulation, and number of oocytes between the groups. Patients in the OC pill group had more embryos on day 3 and more patients had excess embryos for freezing. The number of embryos transferred and clinical pregnancy rates (PR) were similar between the two groups, although more patients in the NuvaRing group had cycles cancelled for poor stimulation. CONCLUSION(S): There was no significant benefit in patient tolerability or side effects with the NuvaRing versus the OC pill for IVF pretreatment; however, side effects overall were low in both groups. Clinical PRs were similar; however, the NuvaRing group had more cancelled cycles and fewer excess embryos for freezing. CLINICAL TRIAL REGISTRATION: #NCT01298128.

Propecia-induced spermatogenic failure: a report of two cases.

OBJECTIVE: To describe the results of two cases of azoospermia and severe oligospermia in men during and after cessation of finasteride 1 mg. DESIGN: Case report. SETTING: Tertiary-care hospital-based clinic for andrology/male infertility. PATIENT(S): Two patients with azoospermia and severe oligospermia using finasteride 1 mg for hair loss. INTERVENTION(S): Discontinuation of finasteride. MAIN OUTCOME MEASURE(S): Improvement in sperm concentration. RESULT(S): Patient A had documented azoospermia over 1 year and was initially booked for a testicular biopsy. Six months after discontinuation of finasteride 1 mg daily he showed improvement in sperm concentration to 5.5 x 10(6)/mL. Patient B had severe oligospermia with a sperm concentration of 4 x 10(6)/mL. Sperm concentration improved to 6.6 then 18.7 x 10(6)/mL at 3 and 6 months after stopping finasteride. CONCLUSION(S): We report two cases of infertile patients with azoospermia or severe oligospermia who showed significant improvements in sperm concentrations 6 months after the discontinuation of finasteride. In one case, improvement in semen parameters prevented the need for testicular biopsy and corrected the azoospermia. Stopping finasteride in the infertility population may improve semen parameters, and may allow for less invasive fertility treatments.

Elevated day 3 follicle-stimulating hormone/luteinizing hormone ratio >or= 2 is associated with higher rates of cancellation in in vitro fertilization-embryo transfer cycles.

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

Use of metformin for ovulation induction in women who have polycystic ovary syndrome with or without evidence of insulin resistance.

OBJECTIVE: To determine whether women with polycystic ovary syndrome (PCOS) and abnormal insulin levels treated with metformin had different rates of ovulation and pregnancy from women with PCOS and normal insulin levels. METHODS: The outcomes of treatment with metformin in 146 infertile women with PCOS were analyzed using a retrospective cohort study design. Baseline characteristics and initial blood work results were recorded. The follow-up period was three months, and the primary outcome was ovulation. RESULTS: Of the 146 women with PCOS, one third had elevated fasting insulin levels. After treatment with metformin, cumulative rates of ovulation were similar in women with elevated fasting serum insulin levels (48.8%) and those with normal levels (44.7%). Rates of ovulation were also similar in women with normal and abnormal glucose to insulin ratios. There was no difference in cumulative pregnancy rates based on fasting insulin levels. A fasting insulin level above 20 mU/L correlated with an abnormal glucose to insulin ratio (98%). CONCLUSION: In anovulatory women with PCOS, fasting insulin levels and glucose to insulin ratios do not predict the ovulatory response to metformin.