Patients who failed to conceive following an in vitro fertilization cycle can be clustered into different failure causes using gene expression hierarchical analysis†.

The patient's response to an IVF stimulation protocol is highly variable and thus difficult to predict. When a cycle fails, there are often no apparent or obvious reasons to explain the failure. Having clues on what went wrong during stimulation could serve as a basis to improve and personalize the next protocol. This exploratory study aimed to investigate if it is possible to distinguish different failure causes or different follicular responses in a population of nonpregnant IVF patients. Using qRT-PCR, we analyzed a panel of genes indicative of different failure causes in patients who did not achieve pregnancy following an IVF cycle. For each patient, a pool of follicular cells from all aspirated follicles was used as a sample which gives a global picture of the patient's ovary and not a specific picture of each follicle. We performed hierarchical clustering analysis to split the patients according to the gene expression pattern. Hierarchical analysis showed that the population of nonpregnant IVF patients could be divided into three clusters. Gene expression was significantly different, and each cluster displayed a particular gene expression pattern. Follicular cells from patients in clusters 1, 2 and 3 displayed respectively a pattern of gene expression related to large incompetent follicles with a higher apoptosis (over matured), to follicles not ready to ovulate (under mature) and to an excess of inflammation with no visible symptoms. This study reinforces the idea that women often have different response to the same protocol and would benefit from more personalized treatments.

Gene expression analysis of follicular cells revealed inflammation as a potential IVF failure cause.

PURPOSE: Hormonal stimulation prior to IVF influences the ovarian environment and therefore impacts oocytes and subsequent embryo quality. Not every patient has the same response to the same treatment and many fail for unknown reasons. Knowing why a cycle has failed and how the follicles were affected would allow clinicians to adapt the treatment accordingly and improve success rate. This study examines the hypothesis that transcriptomic analysis of follicular cells from failed IVF cycles reveals potential reasons for failure and provides new information on the physiological mechanisms related to IVF failure. METHODS: Follicular cells (granulosa cells) were obtained from IVF patients of four Canadian fertility clinics. Using microarray analysis, patients that did not become pregnant following the IVF cycle were compared to those that did. Functional analysis was performed using ingenuity pathway analysis and qRT-PCR was used to validate the microarray results in a larger cohort of patients. RESULTS: The microarray showed 165 differentially expressed genes (DEGs) in the negative group compared to the pregnancy group. DEGs include many pro-inflammatory cytokines and other factors related to inflammation, suggesting that this process might be altered when IVF fails. Overexpression of several factors, some of which act upstream from vascular endothelial growth factor (VEGF), also indicates increased permeability and vasodilation. Some DEGs were related to abnormal differentiation and increased apoptosis. CONCLUSIONS: Our results suggest that failure to conceive following IVF cycles could be associated with an imbalance between pro-inflammatory and anti-inflammatory mediators. The findings of this study identify potential failure causes and pathways for further investigation. Stimulatory protocols personalized according to patient response could improve the chances of later success.

No. 354-Canadian HIV Pregnancy Planning Guidelines.

OBJECTIVE: The objective of the Canadian HIV Pregnancy Planning Guidelines is to provide clinical information and recommendations for health care providers to assist Canadians affected by HIV with their fertility, preconception, and pregnancy planning decisions. These guidelines are evidence- and community-based and flexible and take into account diverse and intersecting local/population needs based on the social determinants of health. INTENDED OUTCOMES: EVIDENCE: Literature searches were conducted by a librarian using the Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase databases for published articles in English and French related to HIV and pregnancy and HIV and pregnancy planning for each section of the guidelines. The full search strategy is available upon request. VALUES: The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the SOGC under the leadership of the principal authors, and recommendations were made according to the guidelines developed by the Canadian Task Force on Preventive Health Care and through use of the Appraisal of Guidelines Research and Evaluation instrument for the development of clinical guidelines. BENEFITS, HARMS, AND COSTS: Guideline implementation should assist the practitioner in developing an evidence-based approach for the prevention of unplanned pregnancy, preconception, fertility, and pregnancy planning counselling in the context of HIV infection. VALIDATION: These guidelines have been reviewed and approved by the Infectious Disease Committee and the Executive and Council of the SOGC. SPONSOR: Canadian Institutes of Health Research Grant Planning and Dissemination grant (Funding Reference # 137186), which funded a Development Team meeting in 2016.

Canadian HIV Pregnancy Planning Guidelines: No. 278, June 2012.

OBJECTIVE: Four main clinical issues need to be considered for HIV-positive individuals and couples with respect to pregnancy planning and counselling: (1) pre-conceptional health; (2) transmission from mother to infant, which has been significantly reduced by combined antiretroviral therapy; (3) transmission between partners during conception, which requires different prevention and treatment strategies depending on the status and needs of those involved; and (4) management of infertility issues. The objective of the Canadian HIV Pregnancy Planning Guidelines is to provide clinical information and recommendations for health care providers to assist HIV-positive individuals and couples with their fertility and pregnancy planning decisions. These guidelines are evidence- and community-based and flexible, and they take into account diverse and intersecting local/population needs and the social determinants of health. OUTCOMES: Intended outcomes are (1) reduction of risk of vertical transmission and horizontal transmission of HIV, (2) improvement of maternal and infant health outcomes in the presence of HIV, (3) reduction of the stigma associated with pregnancy and HIV, and (4) increased access to pregnancy planning and fertility services. EVIDENCE: PubMed and Medline were searched for articles published in English or French to December 20, 2010, using the following terms: "HIV" and "pregnancy" or "pregnancy planning" or "fertility" or "reproduction" or "infertility" or "parenthood" or "insemination" or "artificial insemination" or "sperm washing" or "IVF" or "ICSI" or "IUI." Other search terms included "HIV" and 'horizontal transmission" or "sexual transmission" or "serodiscordant." The following conference databases were also searched: Conference on Retroviruses and Opportunistic Infections, International AIDS Conference, International AIDS Society, Interscience Conference on Antimicrobial Agents and Chemotherapy, the Canadian Association of HIV/AIDS Research, and the Ontario HIV Treatment Network Research Conference. Finally, a hand search of key journals and conferences was performed, and references of retrieved articles were reviewed for additional citations. Subsequently, abstracts were categorized according to their primary topic (based on an outline of the guidelines) into table format with the following headings: author, title, study purpose, participants, results and general comments. Finally, experts in the field were consulted for their opinions as to whether any articles were missed. 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 (Table) and through use of the Appraisal of Guidelines Research and Evaluation instrument for the development of clinical guidelines. SPONSORS: The Society of Obstetricians and Gynecologists of Canada, Women and HIV Research Program, Women's College Research Institute, Women's College Hospital, University of Toronto, Abbott Laboratories Canada, the Ontario HIV Treatment Network, the Canadian Institutes of Health Research, and the Canadian HIV Trials Network.

Canadian HIV pregnancy planning guidelines.

OBJECTIVE: Four main clinical issues need to be considered for HIV-positive individuals and couples with respect to pregnancy planning and counselling: (1) pre-conceptional health; (2) transmission from mother to infant, which has been significantly reduced by combined antiretroviral therapy; (3) transmission between partners during conception, which requires different prevention and treatment strategies depending on the status and needs of those involved; and (4) management of infertility issues. The objective of the Canadian HIV Pregnancy Planning Guidelines is to provide clinical information and recommendations for health care providers to assist HIV-positive individuals and couples with their fertility and pregnancy planning decisions. These guidelines are evidence- and community-based and flexible, and they take into account diverse and intersecting local/population needs and the social determinants of health. OUTCOMES: Intended outcomes are (1) reduction of risk of vertical transmission and horizontal transmission of HIV, (2) improvement of maternal and infant health outcomes in the presence of HIV, (3) reduction of the stigma associated with pregnancy and HIV, and (4) increased access to pregnancy planning and fertility services. EVIDENCE: PubMed and Medline were searched for articles published in English or French to December 20, 2010, using the following terms: "HIV" and "pregnancy" or "pregnancy planning" or "fertility" or "reproduction" or "infertility" or "parenthood" or "insemination" or "artificial insemination" or "sperm washing" or "IVF" or "ICSI" or "IUI." Other search terms included "HIV" and "horizontal transmission" or "sexual transmission" or "serodiscordant." The following conference databases were also searched: Conference on Retroviruses and Opportunistic Infections, International AIDS Conference, International AIDS Society, Interscience Conference on Antimicrobial Agents and Chemotherapy, the Canadian Association of HIV/AIDS Research, and the Ontario HIV Treatment Network Research Conference. Finally, a hand search of key journals and conferences was performed, and references of retrieved articles were reviewed for additional citations. Subsequently, abstracts were categorized according to their primary topic (based on an outline of the guidelines) into table format with the following headings: author, title, study purpose, participants, results and general comments. Finally, experts in the field were consulted for their opinions as to whether any articles were missed. 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 (Table) and through use of the Appraisal of Guidelines Research and Evaluation instrument for the development of clinical guidelines. SPONSORS: The Society of Obstetricians and Gynaecologists of Canada, Women and HIV Research Program, Women's College Research Institute, Women's College Hospital, University of Toronto, Abbott Laboratories Canada, the Ontario HIV Treatment Network, the Canadian Institutes of Health Research, and the Canadian HIV Trials Network. KEY POINTS AND RECOMMENDATIONS: HIV-positive people who are considering pregnancy should be counselled on the following issues so they can make an informed decision.