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In brief Immune dysfunction may contribute to or cause recurrent implantation failure. This article summarizes normal and pathologic immune responses at implantation and critically appraises currently used immunomodulatory therapies. Abstract Recurrent implantation failure (RIF) may be defined as the absence of pregnancy despite the transfer of ≥3 good-quality blastocysts and is unexplained in up to 50% of cases. There are currently no effective treatments for patients with unexplained RIF. Since the maternal immune system is intricately involved in mediating endometrial receptivity and embryo implantation, both insufficient and excessive endometrial inflammatory responses during the window of implantation are proposed to lead to implantation failure. Recent strategies to improve conception rates in RIF patients have focused on modulating maternal immune responses at implantation, through either promoting or suppressing inflammation. Unfortunately, there are no validated, readily available diagnostic tests to confirm immune-mediated RIF. As such, immune therapies are often started empirically without robust evidence as to their efficacy. Like other chronic diseases, patient selection for immunomodulatory therapy is crucial, and personalized medicine for RIF patients is emerging. As the literature on the subject is heterogenous and rapidly evolving, we aim to summarize the potential efficacy, mechanisms of actions and side effects of select therapies for the practicing clinician.

Recurrent implantation failure (RIF) may be defined as the absence of pregnancy despite the transfer of ≥ 3 good quality blastocysts and is unexplained in up to 50% of cases. There are currently no effective treatments for patients with unexplained RIF. Since the maternal immune system is intricately involved in mediating endometrial receptivity and embryo implantation, both insufficient and excessive endometrial inflammatory responses during the window of implantation are proposed to lead to implantation failure. Recent strategies to improve conception rates in RIF patients have focused on modulating maternal immune responses at implantation, either through promoting or suppressing inflammation. Unfortunately, there are no validated, readily available diagnostic tests to confirm immune-mediated RIF. As such, immune therapies are often started empirically without robust evidence as to their efficacy. Like other chronic diseases, patient selection for immunomodulatory therapy is crucial and personalized medicine for RIF patients is emerging. As the literature on the subject is heterogenous and rapidly evolving, we aim to summarize the potential efficacy, mechanisms of actions and side effects of select therapies for the practicing clinician.

Objective The number of couples experiencing infertility treatment has increased, as has the number of women and men experiencing infertility treatment-related stress and anxiety. Therefore, there is a need to provide information and support to both men and women facing fertility concerns. To achieve this goal, we designed a mhealth app, Infotility, that provided men and women with tailored medical, psychosocial, lifestyle, and legal information. Methods This study specifically examined how fertility factors (e.g. time in infertility treatment, parity), socio-demographic characteristics (e.g. gender, education, immigrant status), and mental health characteristics (e.g. stress, depression, anxiety, fertility-related quality of life) were related to male and female fertility patients’ patterns of use of the Infotility app. Results Overall, the lifestyle section of the app was the most highly used section by both men and women. In addition, women without children and highly educated women were more likely to use Infotility. No demographic, mental health or fertility characteristics were significantly associated with app use for men. Conclusion This study shows the feasibility of a mhealth app to address the psychosocial and informational needs of fertility patients.

To study the effect of increasing endometrial thickness on live birth rates in fresh and frozen-thaw embryo transfer (FET) cycles.Retrospective cohort study.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.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.None.Clinical pregnancy, pregnancy loss, and live birth rates.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.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 thickness6 mm was associated clearly with a dramatic reduction in live birth rates in fresh and frozen embryo transfer cycles.

Objective To provide a comprehensive review and evidence-based recommendations for the delivery of fertility care to women with obesity. Outcomes The impact of obesity on fertility, fertility treatments, and both short and long-term maternal fetal outcomes was carefully considered. Evidence Published literature was reviewed through searches of MEDLINE and CINAHL using appropriate vocabulary and key words. Results included systematic reviews, clinical trials, observational studies, clinical practice guidelines, and expert opinions. Values The Canadian Fertility & Andrology Society (CFAS) is a multidisciplinary, national non-profit society that serves as the voice of reproductive specialists, scientists, and allied health professionals working in the field of assisted reproduction in Canada. The evidence obtained for this guideline was reviewed and evaluated by the Clinical Practice Guideline (CPG) Committee of the CFAS under the leadership of the principal authors. Benefits, Harms, and Costs The implementation of these recommendations should assist clinicians and other health care providers in counselling and providing reproductive care to women with obesity. Validation This guideline and its recommendations have been reviewed and approved by the membership, the CPG Committee and the Board of Directors of the CFAS. Sponsors Canadian Fertility & Andrology Society. Recommendations Twenty-one evidence based recommendations are provided. These recommendations specifically evaluate the impact of obesity on natural fertility, fertility treatments, and maternal-fetal outcomes. Strategies to lose weight and BMI cut-offs are also addressed.

Resume Objectif Mener une revue exhaustive de la litterature sur la congelation d'ovules pour des raisons sociales et formuler des recommandations fondees sur des donnees probantes a l'intention des cliniques de fertilite canadiennes offrant ce service. Resultats Nous avons evalue les taux de survie et de fecondation des ovocytes decongeles, la qualite des embryons et les taux de grossesses et de naissances vivantes obtenus au cours de cycles de congelation d'ovules pour des raisons sociales. Nous avons egalement evalue l'influence de l'âge des femmes, de leur reserve ovarienne et du nombre d'ovules cryoconserves sur ces resultats. Finalement, nous avons aborde les risques lies a la congelation d'ovules pour des raisons sociales, les solutions de rechange, les elements essentiels a prendre en compte lors des consultations avec les patientes et de l'obtention de leur consentement eclaire, ainsi que la production des futurs rapports sur les donnees relatives aux resultats de la congelation d'ovules. Donnees Nous avons examine des etudes publiees recuperees au moyen de recherches dans MEDLINE et CINAHL a l'aide d'une terminologie appropriee et de mots-cles (« oocyte cryopreservation », « egg freezing », « egg vitrification », « social egg freezing », et « elective egg freezing »). Les resultats retenus provenaient de revues systematiques, d'essais cliniques randomises, d'essais cliniques controles et d'etudes observationnelles. Nous nous sommes egalement servis d'avis d'experts reposant sur leur experience clinique, sur des etudes descriptives ou sur des rapports de comites d'experts afin d'aborder les aspects de la congelation d'ovules n'ayant pas encore fait l'objet d'etudes rigoureuses. Valeur Les resultats ont ete examines et evalues par le Comite des lignes directrices de pratique clinique de la Societe canadienne de fertilite et d'andrologie, sous la direction des auteurs principaux. Avantages, inconvenients et couts La mise en œuvre de la presente directive clinique devrait aider les cliniciens a elaborer une approche optimale de consultation sur la congelation d'ovules, tout en reduisant au minimum les effets nefastes et en ameliorant les resultats des patientes durant le traitement. Validation La presente directive clinique a ete revisee et approuvee par les membres et le Comite des lignes directrices de pratique clinique de la Societe canadienne de fertilite et d'andrologie, ainsi que par le Comite sur les directives cliniques de la Societe des obstetriciens et gynecologues du Canada (SOGC). Commanditaires Societe canadienne de fertilite et d'andrologie et SOGC. Recommandations 1.Les patientes devraient etre avisees que le taux de survie des ovocytes decongeles varie, mais qu'il se situe generalement entre 80 % et 90 % (forte, haute). 2.Les ovocytes decongeles devraient etre fecondes par injection intracytoplasmique d'un spermatozoide. Les patientes devraient etre avisees que le taux de fecondation varie, mais qu'il se situe generalement entre 70 % et 80 % (forte, haute). 3.Les patientes devraient etre avisees que les ovocytes vitrifies ne donnent pas autant de blastocystes que les ovocytes frais (faible, moyenne). 4.Les patientes devraient etre avisees qu'il existe tres peu de donnees sur le taux de naissances vivantes obtenues a la suite d'une congelation d'ovules pour des raisons sociales, mais que les donnees actuelles laissent croire que le transfert d'embryons issus d'ovocytes vitrifies et celui d'embryons issus d'ovocytes frais donnent sensiblement le meme taux de grossesses cliniques (forte, moyenne). 5.Les femmes qui envisagent de faire congeler leurs ovules pour des raisons sociales devraient etre avisees que l'âge auquel elles les font congeler et le nombre d'ovules congeles influenceront la probabilite que ces ovules augmentent leur fertilite (forte, moyenne). 6.L'evaluation de la reserve ovarienne devrait etre offerte pour aider a predire le nombre d'ovules qui pourront etre recueillis a la suite d'un cycle de stimulation ovarienne controlee, et pour orienter les conseils fournis aux femmes qui risquent de ne produire qu'un tres faible nombre d'ovules (forte, haute). 7.Les femmes qui envisagent de faire congeler leurs ovules pour des raisons sociales devraient etre avisees que plus d'un cycle peut etre necessaire pour obtenir le nombre d'ovules matures souhaite (forte, haute). 8.Les patientes qui envisagent de faire congeler leurs ovules pour des raisons sociales devraient etre informees des risques lies a la stimulation ovarienne controlee, au prelevement d'ovocytes et a la grossesse a un âge maternel avance (forte, moyenne). 9.Les patientes qui envisagent de faire congeler leurs ovules pour des raisons sociales devraient etre avisees qu'il est possible qu'elles n'aient pas besoin de leurs ovules congeles, et qu'il n'est pas garanti que les ovules congeles donneront lieu a une grossesse viable (forte, haute). 10.Les femmes qui envisagent de faire congeler leurs ovules pour des raisons sociales devraient recevoir des conseils sur les solutions de rechange (forte, moyenne). 11.Les femmes qui choisissent de faire congeler leurs ovules pour des raisons sociales devraient recevoir suffisamment de renseignements pour etre en mesure de donner un consentement eclaire (forte, haute). 12.Les cliniques de fecondation in vitro offrant un service de congelation d'ovules pour des raisons sociales devraient donner aux patientes une estimation de la probabilite de reussite du traitement. Cette estimation doit tenir compte de la litterature medicale publiee, mais egalement des donnees nationales sur la congelation des ovules et des donnees propres a la clinique sur le taux cumulatif de naissances vivantes par prelevement d'ovocytes (forte, basse).

Objective To provide a comprehensive review and evidence based recommendations for Canadian fertility centres that offer social egg freezing. Outcomes In social egg freezing cycles we evaluated thawed oocyte survival rates, fertilization rates, embryo quality, pregnancy rates, and live birth rates. We also review how these outcomes are impacted by age, ovarian reserve, and the number of eggs cryopreserved. Finally, we discuss the risks of social egg freezing, the alternatives, the critical elements for counselling and informed consent, and future reporting of egg freezing outcome data. Evidence Published literature was reviewed through searches of MEDLINE and CINAHL using appropriate vocabulary and using key words ("oocyte cryopreservation," "egg freezing," "egg vitrification," "social egg freezing," and "elective egg freezing"). Results included systematic reviews, randomized controlled trials, controlled clinical trials, and observational studies. Expert opinion based on clinical experience, descriptive studies, or reports of expert committees was also included to discuss aspects of egg freezing not currently rigorously studied. Values The evidence obtained was reviewed and evaluated by the Clinical Practice Guideline (CPG) Committees of the Canadian Fertility and Andrology Society (CFAS) under the leadership of the principal authors. Benefits, Harms, and Costs Implementation of this guideline should assist the clinician to develop an optimal approach in providing counselling for egg freezing while minimizing harm and improving patient outcomes during treatment. Validation These guidelines have been reviewed and approved by the membership of the CFAS and by the CPG Committees of CFAS and The Society of Obstetricians and Gynaecologists of Canada (SOGC). Sponsors CFAS and SOGC. Recommendations 1.Patients should be advised that thawed oocyte survival rates vary, typically between 80% and 90% (Strong, High). 2.Thawed oocytes should be fertilized using intra cytoplasmic sperm injection and patients should be advised that fertilization rates vary, typically between 70% and 80% (Strong, High). 3.Patients should be advised that vitrified oocytes yield fewer blastocysts than fresh oocytes do (Weak, Moderate). 4.Patients should be advised that there are very limited data on live birth rates after social egg freezing, but that the existing data suggest similar clinical pregnancy rates after transfer of embryos obtained by either vitrified or fresh oocytes (Strong, Moderate). 5.Women considering social egg freezing should be advised that the age at which they freeze their eggs and the number of eggs that are frozen impact the probability that these eggs will enhance their fertility (Strong, Moderate). 6.Ovarian reserve testing should be offered to help predict the number of retrievable eggs from a controlled ovarian stimulation cycle and to properly counsel those women at risk of very low oocyte yield (Strong, High). 7.Women considering social egg freezing should be advised that more than one cycle may be required to obtain the number of mature eggs that is desired (Strong, High). 8.Patients considering social egg freezing should be informed about the risks of controlled ovarian stimulation, oocyte retrieval, and pregnancy at a more advanced maternal age (Strong, Moderate). 9.Patients considering social egg freezing should be advised that there is a chance they may not need to use their frozen eggs and that no guarantees can be made that their frozen eggs would produce a viable pregnancy (Strong, High). 10.Women considering social egg freezing should be counselled about the alternative options (Strong, Moderate). 11.Women undergoing social egg freezing should receive sufficient information to provide informed consent (Strong, High). 12.In vitro fertilization centres offering social egg freezing should provide their patients with an estimate of their chances of success. This estimate should not only consider the published medical literature but also should take into account national data regarding social egg freezing and clinic-specific data regarding cumulative live birth rates per oocyte retrieval (Strong, Low).

BACKGROUND Given the complexity of infertility diagnoses and treatments and the convenience of the internet for finding health-related information, people undergoing infertility treatments often use Web-based resources to obtain infertility information and support. However, little is known about the types of information and support resources infertility patients search for on the internet and whether these resources meet their needs. OBJECTIVE The aims of this study were to (1) examine what individual factors, namely, demographic characteristics and distress, are associated with searching the internet for different types of infertility-related information and support resources and (2) determine whether Web-based resources meet the needs of patients. METHODS Men and women seeking infertility care responded to a survey assessing use of Web-based resources for accessing infertility-related information and support. The survey further assessed satisfaction with Web-based resources as well as perceived stress and depressive symptomatology. RESULTS A total of 567 participants, including 254 men and 313 women, completed the survey. Most participants (490/558, 87.8%) had searched the internet for infertility information and support. Searchers were more likely to be women (PP=.04), long-term patients (P=.03), and more distressed (P=.04). Causes of infertility, treatment options, and scientific literature about infertility were the three most frequently searched topics, whereas ways to discuss treatment with family and friends as well as surrogacy and ways to find peer support were the three least searched topics. Of those who searched the internet, 70.9% (346/488) indicated that their needs were met by Web-based information, whereas 29.1% (142/488) said that their needs were not met. Having unmet needs was related to greater levels of perceived stress (P=.005) and depressive symptomatology (P=.03). CONCLUSIONS This study provides evidence for the important role of the internet in accessing infertility information and support and for the ability of Web-based resources to meet patients’ needs. However, although distressed patients reported particularly high rates of searching, their needs were not always met, suggesting that they may benefit from alternative sources of information and support or guidance from health care providers when searching the internet.