Committee Opinions Research Articles

Clinical Evidence Supporting FDA Approval of Gene and RNA Therapies for Rare Inherited Conditions.

Gene and RNA therapies have potential to transform the treatment of rare inherited diseases, but there are concerns about the evidence supporting their use and high costs. We analyze the evidence supporting Food and Drug Administration (FDA) approval of gene and RNA therapies for rare inherited diseases and discuss implications for clinical practice and policy. We conducted a qualitative analysis of FDA documents outlining the basis of approval for gene and RNA therapies approved for rare inherited diseases between 2016 and 2023. For each drug, we gathered five characteristics of the evidence supporting FDA approval (no phase 3 trial, nonrandomized, no clinical endpoint, lack of demonstrated benefit, and significant protocol deviation) and four characteristics of the FDA approval process (prior rejection or complete response, negative committee vote, discrepancy between label and trial population, and boxed warning). The main outcome was the number of drugs with each characteristic. Between 2016 and 2023, 19 gene and RNA therapies received FDA approval to treat rare inherited diseases. The most common limitations in the evidence supporting approval of these drugs were nonrandomized studies (8/19, 42%), no clinical endpoint (7/19, 37%), lack of demonstrated benefit or inconsistent results (4/19, 21%), and no phase 3 trial (4/19, 21%). Half (3/6) of accelerated approvals and 57% (5/9) of drugs with breakthrough designation had nonrandomized trials, and gene therapies with one-time dosing were overrepresented (5/7, 71%) among the drugs with nonrandomized trials. Five of six accelerated approvals (83%) and five of nine pediatric drugs (56%), most of which were indicated for Duchenne muscular dystrophy, had no clinical endpoint. Four of nine (44%) pediatric drugs and four of six (67%) accelerated approvals failed to demonstrate benefit compared with none of the nonpediatric drugs and none of the traditional approvals. Five drugs, which all had different indications and represented a mix of RNA and gene therapies, did not have any of these evidence characteristics. Among drugs that received prior rejections or negative committee opinions, all four had nonrandomized trials and lacked a clinical endpoint, and 75% (3/4) lacked demonstrated benefit. Five of nine (56%) pediatric drugs were indicated for broader age groups according to the drug label compared with the trial populations. Of the three drugs with boxed warnings, two had pediatric indications and nonrandomized studies, and one had no phase 3 trial. Issues related to trial design, outcome, and data integrity in the evidence supporting FDA approval of rare inherited disease gene and RNA therapies raise questions about whether this evidence is adequate to inform prescribing decisions. Gene and RNA therapies with accelerated approval and pediatric indications were overrepresented among drugs lacking clinical endpoints or demonstrated benefit and should be the focus of efforts to reduce uncertainty in the evidence.

Evaluation of the Ability to Sing Easily: Adaptation and validation to the European Portuguese language

Purpose: To adapt and validate the Evaluation of the Ability to Sing Easily (EASE) to the European Portuguese language; to compare scores according to singing style, voice use, and demography variables; to conduct psychometric tests. Methods: A five-step approach was adopted to ensure the cross-cultural adaptation of the instrument including forward translation, backward translation, committee opinions, and pilot testing. Results: The pilot test was conducted with ten singers, which determined the reformulation of seven items, thereby, allowing the formulation of the final form. The EASE-PT was completed by 120 singers, age range 18–72 and 58.3% were female. Median results were significantly higher for Choir singers except for one item where the median was significantly higher for Fado singers. High internal consistency was obtained, Cronbach’s alpha > 0.80 for EASE scale for both Fado and Choir singers, and its sub scales were close to or exceeded 0.80. Conclusion: EASE-PT may be considered a reliable tool to apply in the case of Portuguese singers as the outcome supports the ability of EASE-PT to measure the same constructs in a way similar to that of the original version.

A systematic review of assisted and third-party reproduction guidelines regarding management and care of donors

BackgroundGamete and embryo donors face complex challenges affecting their health and quality of life. Healthcare providers need access to well-structured, evidence-based, and needs-based guidance to care for gamete and embryo donors. Therefore, this systematic review aimed to synthesize current assisted and third-party reproduction guidelines regarding management and care of donors.MethodsThe databases of ISI, PubMed, Scopus, and websites of organizations related to the assisted reproduction were searched using the keywords of “third party reproduction”, “gamete donation”, “embryo donation”, “guidelines”, “committee opinion”, and “best practice”, without time limit up to July 2023. All the clinical or ethical guidelines and best practice statements regarding management and care for gamete and embryo donors written in the English language were included in the study. Quality assessment was carried using AGREE II tool. Included documents were reviewed and extracted data were narratively synthesized.ResultsIn this systematic review 14 related documents were reviewed of which eight were guidelines, three were practice codes and three were committee opinions. Five documents were developed in the United States, three in Canada, two in the United Kingdom, one in Australia, and one in Australia and New Zealand. Also, two guidelines developed by the European Society of Human Reproduction and Embryology were found. Management and care provided for donors were classified into four categories including screening, counseling, information provision, and ethical considerations.ConclusionWhile the current guidelines include some recommendations regarding the management and care of gamete/embryo donors in screening, counseling, information provision, and ethical considerations, nevertheless some shortcomings need to be addressed including donors’ psychosocial needs, long-term effects of donation, donors’ follow-up cares, and legal and human rights aspects of donation. Therefore, it is needed to conduct robust and well-designed research studies to fill the knowledge gap about gamete and embryo donors’ needs, to inform current practices by developing evidence-based guidelines.

The Role of the World Heritage Convention for Foreign Investments and Investment Disputes: An Overlooked Instrument for Preventing Harmful Investment Activities?

Investment activities by foreign investors such as mining operations or energy production can threaten natural and cultural World Heritage, which is protected under the World Heritage Convention. As World Heritage sites have been at the heart of various (recent) investment disputes, the question arises as to how obligations under the World Heritage Convention affect investment activities and investment disputes. The article seeks to shed light on this issue by analysing different aspects of the World Heritage Convention in the context of investment law. It starts by exploring how investment tribunals have approached investment disputes involving World Heritage sites and what their decisions imply for the regulation of investment activities in or near World Heritage sites. Subsequently, the article examines which obligations the World Heritage Convention imposes on foreign investors, host states, and investors‘ home states. In the analysis of the home states‘ duties, Article 6(3) of the Convention, which has hitherto received little scholarly attention, is of particular interest. Based on decisions of the World Heritage Committee and doctrinal opinions, the authors interpret said provision and place it in the specific context of investment law. In doing so, they find that a limited duty to regulate exists for home states of investors if they provide financial or non-financial support to a business operation abroad.

HTA202 Learnings From First TC Opinions of Drugs Evaluated for EAP Under New Process

In France, patients can benefit an early access to innovation, ahead of the marketing authorization or final reimbursement, since 1992. This early access program (EAP) was reformed on July 1, 2021. The new process involves a joint assessment by ANSM and HAS. Thus, HAS is now involved in granting EAP (HAS decision) while continuing to assess drugs for reimbursement (Transparency Committee (TC) opinions). According to HAS, this ensures consistency between derogation-based schemes (EAP) and the common law funding scheme (based on TC opinions). This study aimed at analyzing TC opinions for reimbursement of drugs which have also been assessed for EAP with new process.

HTA209 Comparative Analysis of the Transparency Committee Opinions Concerning the Added Medical Benefit Levels Depending on the Therapeutic Areas: Distribution of Innovation and Trend Assessment for 2016-2021

The aim of this research was to analyse the distribution of innovation over the last 6 years, based on the therapeutic areas and the added medical benefit (ASMR) issued by the HAS transparency committee (TC).

Guidelines for Cystic Fibrosis Carrier Screening in the Prenatal/Preconception Period.

Cystic fibrosis (CF) is one of the most common autosomal recessive disorders. Carrier screening for CF should be offered to all women considering becoming pregnant or who are pregnant. Understanding the available screening tests, their limitations, and the benefits of screening is of paramount importance to the obstetrician-gynecologist. The objective is to review the current guidelines for CF carrier screening including the options for carrier screening, the potential complexities associated with carrier screening for CF, and indications for referral to certified genetic counselors or maternal-fetal medicine specialists. A MEDLINE search of "cystic fibrosis," "cystic fibrosis carrier screening pregnancy," and "inheritance of cystic fibrosis" in the review was performed. The evidence cited in this review includes 2 medical society committee opinions and 15 additional peer-reviewed journal articles that were original research or expert opinion summaries. The American College of Obstetricians and Gynecologists recommends that obstetricians offer CF carrier screening to all pregnant women or women considering becoming pregnant. Based on recent guidelines from ACMG, additional expanded carrier screening can be recommended to patients in the future, with additional CF variants and other autosomal or X-linked recessive conditions. It is important for the prenatal care provider to understand the guidelines for carrier screening as well as the potential complexities associated with carrier screening due to the multiple pathogenic variants in the CFTR gene that may be associated with varying phenotypes. With the options for CF carrier screening, screening performance in different populations, a basic understanding of the disease and interpretation of carrier screening results is of paramount importance to the prenatal care provider.

Fertility preservation in transgender men and the need for uniform, comprehensive counseling

ObjectiveTo review the literature to assess best practices for counseling transgender men who desire gender-affirming surgery on fertility preservation options.DesignA scoping review of articles published through July 2021.SettingNone.Patient(s)Articles published in Cochrane, Web of Science, PubMed, Science Direct, SCOPUS, and Psychinfo.Intervention(s)None.Main Outcome Measure(s)Papers discussing transgender men, fertility preservation (FP), and FP counseling.Result(s)The primary search yielded 1,067 publications. After assessing eligibility and evaluating with a quality assessment tool, 25 articles remained, including 8 reviews, 5 surveys, 4 consensus studies, 3 retrospective studies, 3 committee opinions, and 2 guidelines. Publications highlighted the importance of including the following topics during counseling: (1) FP and family building options; (2) FP outcomes; (3) effects of testosterone therapy on fertility; (4) contraception counseling; (5) attitudes toward family building; (6) consequences of transgender parenting; and (7) barriers to success.Conclusion(s)Currently, there is a lack of standardization for comprehensive counseling about FP for transgender men. Standardized approaches can facilitate conversation between physicians and transgender men and ensure patients are making informed decisions regarding pelvic surgery and future family building plans.

Changing Tocolytic Exposures among Neonatal Intensive Care Unit Admitted Preterm Infants.

Since 2010, the American College of Obstetrics and Gynecology have released three committee opinions to recommend and reaffirm the utility of magnesium sulfate for neuroprotection and later for tocolysis to achieve antenatal steroid course completion in preterm labor. We sought to determine changes in antenatal magnesium sulfate exposure and other tocolytic agents for pregnancies resulting in neonatal intensive care unit (NICU)-admitted preterm infants. Using the Pediatrix Clinical Data Warehouse, we evaluated all inborn infants delivered between 22 and 33 weeks' gestation and admitted to the intensive care units from 2009 to 2018. We classified patients based on antenatal exposure to tocolytic medications: calcium channel blockers (nifedipine and amlodipine), betamimetics (terbutaline, theophylline, and ritodrine), prostaglandin inhibitors (indomethacin), and magnesium sulfate. A total of 229,781 patients met inclusion criteria. During the study period, magnesium sulfate exposure increased from 27.6 to 57.7% of births while betamimetic exposure decreased from 10.2 to 5.2%. Increasing magnesium sulfate exposure over time was seen at all gestational ages examined and magnesium exposure was most common between 23 and 31 weeks' gestation. By 2017 to 2018, 70.5% of 24 to 29 weeks' gestation NICU infants received exposure to at least one tocolytic agent while this remained at 53.7% of 32 to 33 weeks' NICU admitted infants. Antenatal steroid exposure increased from 74.8 to 87.4% during the study period. For NICU-admitted preterm infants, prenatal exposure patterns to tocolytic agents has shifted since 2009 with prenatal magnesium sulfate exposure increasing significantly. Antenatal steroid exposure has risen concurrently. Exposure to tocolytic agents is the highest among preterm infants born between 24 and 29 weeks' gestation. · Exposure to magnesium sulfate significantly increased from 2009 to 2018 for NICU admitted infants.. · Concurrently, the use of other tocolytics decreased significantly.. · The use of antenatal steroids has been rising over time..

Incorporation of randomized controlled trials into organizational guidelines for obstetricians and gynecologists.

BackgroundThe American College of Obstetricians and Gynecologists publishes practice bulletins and committee opinions to serve as clinical guidelines for physicians. The objective of this study was to quantify the frequency that randomized controlled trials become incorporated into the American College of Obstetricians and Gynecologists documents (either practice bulletins or committee opinions).MethodsOriginal research articles published in The American Journal of Obstetrics and Gynecology, The Journal of the American Medical Association, The New England Journal of Medicine, and Obstetrics and Gynecology between 2009 and 2014 were examined and randomized controlled trials (RCT) in obstetrics and gynecology were identified. Adjusted odds ratio (aOR) with 95% confidence intervals (CI) were calculated to examine the factors associated with a citable RCT being referenced versus not in ACOG documents.ResultsOf the 306 randomized controlled trials identified 248 (81.0%) met the inclusion criteria, with 128 (51.6%) of eligible RCT being cited The factors which increased the likelihood of a RCT being referenced, versus not being, were: if device or surgery was the intervention (aOR 3.60; 95% CI 1.85–7.00) and if the sample size of the trial was 500–999 (aOR 3.70 (1.39–9.82). The following factors were not associated with whether the RCT was or was not referenced in the ACOG documents: topic was obstetric or gynecologic, the trial was conducted in the US or abroad, multi- or single center, year of publication and the journal.ConclusionSince about half of the citable randomized controlled trials published in obstetrics and gynecology are incorporated into ACOG practice bulletins and committee opinions a greater transparency is warranted as to why RCTs are or are not referenced.

Observational and clinical evidence that plant-based nutrition reduces dietary acid load.

Contemporary diets in Western countries are largely acid-inducing and deficient in potassium alkali salts, resulting in low-grade metabolic acidosis. The chronic consumption of acidogenic diets abundant in animal-based foods (meats, dairy, cheese and eggs) poses a substantial challenge to the human body's buffering capacities and chronic retention of acid wherein the progressive loss of bicarbonate stores can cause cellular and tissue damage. An elevated dietary acid load (DAL) has been associated with systemic inflammation and other adverse metabolic conditions. In this narrative review, we examine DAL quantification methods and index observational and clinical evidence on the role of plant-based diets, chiefly vegetarian and vegan, in reducing DAL. Quantitation of protein and amino acid composition and of intake of alkalising organic potassium salts and magnesium show that plant-based diets are most effective at reducing DAL. Results from clinical studies and recommendations in the form of expert committee opinions suggest that for a number of common illnesses, wherein metabolic acidosis is a contributing factor, the regular inclusion of plant-based foods offers measurable benefits for disease prevention and management. Based on available evidence, dietary shifts toward plant-based nutrition effectively reduces dietary-induced, low-grade metabolic acidosis.

Impact of Maternal-Fetal Medicine Unit Networks’ publications on ACOG guidelines

Maternal-Fetal Medicine Units (MFMU) Network was created in 1986 to conduct well-designed trials. We sought to evaluate the impact of the Network’s publications on recommendations by ACOG—in obstetric practice bulletins (PB) and committee opinions (CO)—and with evaluative bibliometrics.

Publication Rates and Citations in Practice Guidelines from R01 Grants in Obstetrics

NIH funding to OBGYN departments represents a core inequity: 1% of the $14.3 billion in NIH funding is designated to OBGYN (Rice LW et al 2020). Thus, it is important to ascertain the rate of publications from NIH funded Research Project Grants (R01). The purpose of this study was to assess the extent to which R01 grants in obstetrics result in publications and incorporation into ACOG practice bulletins (PB) or committee opinions (CO).

The evolving role of the Women's Health Specialist in cancer prevention and survivorship.

This review provides a framework for primary care physicians, internists, family doctors, NP's, PA's, and oncologists caring for women-henceforth referred to as Women's Health Specialists-to identify and screen patients who may be at high risk for inherited cancer syndromes; an intervention referred to as previvorship care. For women who undergo risk-reducing oophorectomy, survivorship care is critical to optimizing quality of life thereafter. In this paper, we review management of the unique survivorship needs and management options for women at risk for or with a cancer diagnosis, highlighting the importance of interdisciplinary care. To review the available previvorship and survivorship management strategies, a Pub Med search was performed using keywords "survivorship," "genetics," "cancer," "menopause," "hormone therapy," "screening" in addition to review of guidelines, position statements and expert, and committee opinions from the American College of OBGYN, the American Society of Clinical Oncology, The North American Menopause Society, the National Comprehensive Cancer Network , and the American Society for Reproductive Medicine. Women's Health Specialists are in a unique position to identify and screen women who may be at risk for inherited cancer syndromes as well as provide necessary survivorship management following transition from their oncologists' care.

Leveraging American College of Obstetricians and Gynecologists Guidelines for Point-of-Care Decision Support in Obstetrics.

The American College of Obstetricians and Gynecologists (ACOG) provides numerous narrative documents containing formal recommendations and additional narrative guidance within the text. These guidelines are not intended to provide a complete "care pathway" for patient management, but these elements of guidance can be useful for clinical decision support (CDS) in obstetrical and gynecologic care and could be exposed within electronic health records (EHRs). Unfortunately, narrative guidelines do not easily translate into computable CDS guidance. This study aimed to describe a method of translating ACOG clinical guidance into clear, implementable items associated with specific obstetrical problems for integration into the EHR. To translate ACOG clinical guidance in Obstetrics into implementable CDS, we followed a set of steps including selection of documents, establishing a problem list, extraction and classification of recommendations, and assigning tasks to those recommendations. Our search through ACOG clinical guidelines produced over 500 unique documents. After exclusions, and counting only sources relevant to obstetrics, we used 245 documents: 38 practice bulletins, 113 committee opinions, 16 endorsed publications, 1 practice advisory, 2 task force and work group reports, 2 patient education, 2 obstetric care consensus, 60 frequently asked questions (FAQ), 1 women's health care guidelines, 1 Prolog series, and 9 others (non-ACOG). Recommendations were classified as actionable (n = 576), informational (n = 493), for in-house summary (n = 124), education/counseling (n = 170), policy/advocacy (n = 33), perioperative care (n = 4), delivery recommendations (n = 50), peripartum care (n = 13), and non-ACOG (n = 25). We described a methodology of translating ACOG narrative into a semi-structured format that can be more easily applied as CDS in the EHR. We believe this work can contribute to developing a library of information within ACOG that can be continually updated and disseminated to EHR systems for the most optimal decision support. We will continue documenting our process in developing executable code for decision support.

Spinal Muscular Atrophy: Inheritance, Screening, and Counseling for the Obstetric Provider.

Spinal muscular atrophy (SMA) confers significant risk of neonatal and infant morbidity and mortality. Screening women during or before pregnancy for carrier status of SMA presents an opportunity to identify pregnancies at risk for this potentially devastating condition. The objective of this review is to describe the different forms of SMA and their inheritance. In addition, this review guides obstetric providers in interpreting results of carrier screening. A MEDLINE search of "prenatal genetic testing," "spinal muscular atrophy," and "inheritance of spinal muscular atrophy" in the review was performed. The evidence cited in this review includes 4 medical society committee opinions and 14 additional peer-reviewed journal articles that were original research or expert opinion summaries. Spinal muscular atrophy is a severe, heterogeneous neurodegenerative disorder. The American College of Obstetricians and Gynecologists recommends that obstetricians offer carrier screening for SMA to all pregnant women. Given the different types and inheritance of SMA, understanding of the disease and interpreting carrier screening results is of paramount importance to the prenatal care provider.

PDG57 LEVEL of Innovation According to Therapeutic Areas As per TC Opinions

The aim of this analysis was to identify the levels of innovations according to therapeutic areas as per to the Transparency Committee (TC) opinions. The new drugs evaluated on initial registration between January 2017 and March 2020 were selected and sorted by major therapeutic areas (neurology, oncology, infectiology, cardiology, endocrinology & metabolism). The classification in therapeutic areas was made from ATC codes to the exception of Radiopharmaceuticals for diagnostic use (ATC code: V09) which were classified based on the indications (some were classified in oncology and others in endocrinology and metabolism). Then the attributed “medical benefit” (SMR) and “added medical benefit” (ASMR) levels in each of the therapeutic areas was counted. The sample contained 178 drugs evaluated for 204 indications. Most of the SMRs granted by the TC were important (65%), mainly in oncology (35%) and infectiology (25%). Only 8 moderated SMR were granted in neurology and oncology and 16 low SMR in cardiology (31%), oncology (50%) and endocrinology & metabolism (19%). On the other hand, 24% of the indications evaluated obtained an insufficient SMR leading to only 156 levels of ASMR being granted. According to the TC, 10% of the indications were innovative (ASMR I to III) and these innovations are more prevalent in oncology (14% of the indications evaluated in oncology) and equivalent in other therapeutic areas (5 to 8%). The TC recognized an added value in innovative therapeutic areas, mainly in oncology (8/14 of ASMR III and 15/39 of ASMR IV). On the contrary, it seems more difficult to be innovative in the other therapeutic areas.

PDG72 Comparative Analysis of the Transparency Committee Opinions Concerning the Added Medical Benefit of Drugs Available through an EARLY Access Programs VS Others Drugs in France: 2020 Update and TREND Assesment

The aim of this research was to update the analysis previously published about comparison of the distribution of the added medical benefit levels (ASMR) issued by the HAS transparency committee (TC) depending on the early access status (ATU or not) in France. The TC opinions concerning a first application for reimbursement inscription adopted between January 2016 and March 18th, 2020 were analyzed. Medicines assessed through simplified procedures and applications resubmitted after a previous withdrawal or a previous negative opinion were excluded. 228 TC opinions on 225 medicines met the inclusion criteria: of them, 72 medicines available through ATU (vs 64 previously) were assessed for the “Added Medical benefit” (81 ASMR, one per indication vs 73 previously) vs 124 medicines (98 previously) that were not available through early access program (127 ASMR vs 100 previously). Fifteen (20.8%) medicines available through ATU (vs 22% previously) were granted an ASMR considered as innovative (0 ASMR I (major), 3 ASMR II (important), 12 ASMR III(moderate)) vs 6 (4.8% vs 4.1% previously) medicines without early access (1 ASMR I, 1 ASMR II and 4 ASMR III). Twenty-six (36.1% vs 34% previously) drugs received a unique minor ASMR IV for medicines available in early access vs 20 (16.1% vs 15% previously) in the group without early access. Twenty-four (33.3% vs 33% previously) drugs received no ASMR in the group of medicines in ATU vs 98 (79.0% vs 80.6% previously) in the group without early access. Twelve drugs (vs 11 previously) were granted with two ASMR. This extended analysis confirms the trend already observed last year. Medicines which have been the subject of an early access program were indeed more likely to obtain an ASMR considered as innovative and a better “rating” for ASMR than the medicines which were not in early access.

PDG71 Comparative Analysis of the Transparency Committee Opinions Concerning the Medical Benefit of Drugs Available in EARLY Access Programs VS Other Drugs in France: 2020 Update and TREND Assesment

The aim of this research was to update the analysis published last year about the comparison of the distribution of the medical benefit levels (SMR) issued by the HAS transparency committee (TC) depending on the early access status (ATU or not) in France. All the TC opinions concerning a first inscription to the reimbursement adopted between January 2016 and March 3rd, 2020 were analyzed. In the selected time period, 228 TC opinions (vs 188 last year) met the inclusion criteria, concerning 225 drugs: for the 75 medicines available through ATU (vs 67 last year) with 92 “Medical benefit” (vs 83 last year) evaluated (one per indication) vs 170 (vs 134 last year) for the 150 medicines without early access (vs 118 last year). “Medical benefit” determines if the medicine is reimbursed or not as well as the rate of reimbursement by the national health insurance (important: 65%; moderate: 30%; low:15%). Ninety-six percent (72/75) (vs 96% last year) of medicines available in the early access program had a favorable reimbursement decision with a sufficient medical benefit for at least one of its indications (68 important, 5 moderate, 7 low) vs 83% (124/150) vs (83% last year) of medicines not available through early access with a sufficient medical benefit (104 important, 8 moderate, 16 low). Medicines available through the ATU program received 12 insufficient medical benefit (13%) vs 42 for medicines not available through ATU (25%). This extended analysis confirms the trend already observed last year. Medicines which benefited from an early access program were more likely to obtain a favorable reimbursement decision and a better “rating” for medical benefit than the others. High unmet medical need (no alternative), common criterion to obtain an ATU and a sufficient medical benefit, could explained the difference observed between the two groups.

Preconception Evaluation Before In Vitro Fertilization.

Infertility poses a substantial public health problem for women of reproductive age, in the United States and globally. Infertility can be overcome with a variety of emerging assisted reproductive technologies (ARTs). In vitro fertilization (IVF) currently represents the most commonly utilized method of ART and is typically associated with the highest clinical pregnancy rate and live birth rate compared with other infertility treatment options. However, proper preconception evaluation and counseling is paramount for optimizing IVF and pregnancy outcomes. This article aims to outline current guidelines and recommendations for comprehensive preconception evaluation before initiation of IVF. Articles were obtained from PubMed, ACOG committee opinions 781 and 762, and relevant textbook chapters. A variety of recommendations and best practices exist for optimally managing patients seeking IVF. Special attention must be paid to the workup of certain patient populations, such as those with age older than 35 years, uterine abnormalities, comorbidities (especially hypertension, diabetes, and thrombophilias), and obesity. In addition, many lifestyle factors must be addressed before IVF initiation, such as smoking, illicit drug use, and inadequate nutrition. Preconception counseling and expectation management is key to optimizing pregnancy outcome. A myriad of patient and environmental factors impact the potential success rates of IVF in treating infertility. Providers must be equipped to provide data-driven, patient-centered counseling before initiation of IVF.