Clinical Research Directory

Automation of the In Vitro Fertilization Laboratory

Enrolled patients will undergo an Assisted Reproductive technology (ART) treatment using intracytoplasmic sperm injection (ICSI, the direct injection of a single sperm cell into an oocyte) as the method of insemination. In this prospective cohort study, patients' sperm, eggs, and embryos will be processed using an automated system called AURA (Conceivable Life Sciences), which consists of five subsystems. Specifically, sperm samples will be prepared for fertilization using the subsystem C:SPERM. Cumulus-oocyte complexes (COCs) containing the oocytes will be isolated from follicular fluid using the subsystem C:EGG. One out of every four COCs will be removed from the AURA system at random and processed according to the local treatment clinic's standard operating procedure. All other COCs will continue automated procedures and will be denuded, fertilized, incubated, and vitrified using the AURA subsystems C:EGG. C:ICSI, C:CULTURE and C:VIT, respectively. All automated procedures will be conducted under the supervision of a laboratory manager, who can intervene, address any potential anomalies, and override any steps undertaken by the automated AURA system. The study aims to deliver a descriptive evaluation of the AURA system, including assessing the device's performance, defined by its level of automation, efficiency, and throughput. As a secondary objective, the study aims to characterize the clinical performance of each of AURA's subsystems and correlate this performance against pre-established benchmarks in a non-inferiority statistical analysis. Finally, the study seeks to collect technical data related to AURA's hardware and software operation.

Standardization of Variable Conditions of Embryo Transfer Into the Uterine Cavity in the Procedure of Medically Assisted Procreation in Humans

The EFECT study is a clinical trial designed to determine whether improving the consistency of embryo transfer procedures can increase pregnancy success in patients undergoing frozen embryo transfer (cryoET). While laboratory techniques for fertilization, embryo culture, and selection have advanced significantly, the process of transferring embryos to the uterus remains variable and depends on small procedural differences, such as temperature changes, mechanical forces, timing, and individual operator techniques. These variations may affect embryo survival and implantation, ultimately influencing pregnancy outcomes. This study tests whether using specialized devices to standardize key aspects of embryo transfer-specifically temperature stability during transport and controlled, precise embryo aspiration and expulsion speed, optimal fluid volume, programmed injection time, elimination of pressure fluctuations and plunger backflow, prevention of embryo re-aspiration and detection of transfer catherer oclusion-can improve pregnancy rates. All embryos in the study are cultured using time-lapse monitoring and selected using artificial intelligence-supported grading, ensuring uniform quality for all participants. The study compares standard manual embryo transfer with transfer using one or both of the devices: Embryocase, which maintains a stable temperature during transport, and Embryopass, which standardizes the procedure and eliminates human factor. A total of 160 participants are randomly assigned to one of four groups: manual transfer without device support, manual transfer with Embryocase, transfer with Embryopass, or transfer with both devices. Participants and outcome assessors are blinded to group assignment, while the staff performing the transfer are aware due to the nature of the devices. All participants receive standard luteal phase support with progesterone following routine clinical practice. The study's main goal is to evaluate whether these procedural improvements lead to higher rates of biochemical pregnancy (positive pregnancy test) and clinical pregnancy (confirmed by ultrasound). Secondary outcomes include implantation rate, live birth rate, device safety, and ease of use as reported by staff. Pregnancy outcomes, including delivery, pregnancy loss, or ectopic pregnancy, are followed until the end of pregnancy. By investigating the impact of procedural standardization, this study aims to determine whether technological improvements during embryo transfer can increase the effectiveness of assisted reproductive treatments. If successful, the results could support the broader adoption of standardized, device-assisted embryo transfer protocols in fertility clinics, helping more patients achieve successful pregnancies.

Delivery Optimization for Pre-Exposure Prophylaxis (DO PrEP) Study

The overall goal is to determine whether an end-to-end decentralized delivery service for PrEP is more effective, safe, acceptable, and cost-effective than facility-based PrEP delivery.

Use of Artificial Intelligence for Clinical Assessment of Assisted Reproductive Techniques and IVF Outcomes

The use of machine learning techniques using an artificial intelligence tool is proposed to analyze clinical data to predict best possible IVF/ART outcomes. This tool has been utilized to accurately predict embryo quality here at Cornell. Utilizing this tool to assess objective clinical findings and predict outcomes of assisted reproductive techniques is sought, with the ultimate goal of an automated tool to reduce implicit physician bias. Within this goal, using this tool to objectively and accurately assess baseline ovarian reserve at the start of an ART cycle is proposed, using 3D sonography to image the ovary and artificial intelligence tool to objectively identify baseline antral follicle counts.

Enhancing Management Algorithms for Children Conceived Via Assisted Reproductive Technologies

Research Methods and Ethical Issues 1. Main Scientific Questions and Hypotheses of the Project The primary objective of this project is to investigate the impact of advanced ART methods on the health status of children. The central scientific questions being addressed include: What are the consequences of ICSI and FET on the physical, cognitive, and reproductive health of children? The underlying hypothesis posits that children conceived by advanced ART methods may present with health indicators that deviate from the established norms. 2. Description of the Experiments Research Methods: To achieve the goals of the study, the following stages are anticipated: 1. Retrospective Analysis of Anamnestic Data: This stage involves studying the relationship between the physical status and morbidity structure of 300 children under the age of three, who were conceived by advanced ART methods. Additionally, the medical history of their mothers regarding the use of various medications during pregnancy-such as estrogen, progesterone, thyroid hormones, antithyroid hormones, vitamins, microelements, and aspirin-will be examined. To facilitate this analysis, individual registration cards will be developed, approved by the ethics committee, and ratified by the Academic Council. The data will be submitted using Google Forms, followed by the inclusion of copyright information into the state register. 2. Evaluation of Anthropometric Data: This stage will assess the anthropometric data of 300 children under three years of age, focusing on those born after FET or fresh embryo transfer (Fresh-ET). Measurements will include weight, height, and head and chest circumference at the time of examination. Measurements for children under one year will utilize scales with a pan balance, a horizontal stadiometer, and a measuring tape. For children over one year, floor electronic scales, a vertical stadiometer, and a centimeter tape will be employed. Birth anthropometric data will be sourced retrospectively, while the WHO Child Growth Standards will be utilized to evaluate weight, height, head, and chest circumference relative to age and gender. 3. Study of Psychomotor Development: The psychomotor development of the 300 children under three years of age conceived via IVF or ICSI in fresh or frozen cycles will be assessed. This evaluation will employ standardized instruments such as the R. Griffiths Mental Development Scale and Denver Developmental Screening Tests. For children under one year, neurosonography will be conducted to assess brain structures, and retrospective results for children over one year of age will be extracted from medical records. The assessment aims to determine the functions of the nervous system utilizing the aforementioned standardized scales, focusing on various developmental parameters, including motor skills, social adaptation, communication abilities, and play skills. Scores will be compiled to ascertain overall developmental levels. The Denver II developmental screening test is specifically designed to assess children from birth to six years of age. It enhances diagnostic capabilities and evaluates several critical parameters, including: 1) personal and social characteristics, which examine the child's interactions with others and their ability to meet personal needs; 2) the development of gross and fine motor skills; 3) the development of both motor and sensory speech; and 4) an assessment of the child's behavior during the evaluation process. In cases where children are identified as being in the "risk group," a consultation with a neurologist is planned to establish examination protocols and identify the etiopathogenetic basis for potential developmental disorders. Standard methods of neurological examination will be utilized to assess the development of motor, sensory, cognitive, speech, emotional, communicative, and behavioral parameters in conjunction with anamnestic data and the overall state of somatic health. 4. Assessment of Reproductive Health: The study will also evaluate the effect of ICSI, particularly in cases of male infertility, on the reproductive health and development of 200 male children under three years of age, in comparison with children conceived via classic IVF. This evaluation will involve objective examinations conducted by a pediatric andrologist to investigate the prevalence of urogenital pathology, supplemented by ultrasounds of the scrotum, kidneys, and bladder. Additionally, hormonal status will be assessed by Inhibin B and Anti-Müllerian Hormone (AMH). Anamnestic data will be collected to explore the relationship between the reproductive health of fathers and their sons born after ICSI. 3\) Methods of Data Collection and Processing Data Collection Sources of Information: Data will be sourced from the International clinical center of the reproductology "PERSONA" and Institute of Reproductive Medicine (IRM clinic), in addition to direct examinations of participants based

PRIOR Study (Pre-eclampsia Risk In Oocyte Recipients)

The aim of this prospective observational cohort study is to investigate the pathophysiological mechanisms behind and risk of pre-eclampsia in women pregnant after fertility treatment with oocyte donation. The participants are included in of of two cohorts. One includes women pregnant after oocyte donation whereas the other includes women pregnant after IVF treatment with autologous oocytes. Participants will be followed throughout pregnancy with blood samples, blood pressure, clinical controls and ultrasound examinations. Clinical outcomes will be registered post-partum.

RV630 - Approach to Control HIV With Immune Enhancement and Vaccination (ACHIEV

This is a phase I, randomized, double-blind, placebo-controlled clinical trial to investigate the safety of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62 prime, MVA.tHIVconsv4 and A244d11gp120/ALFQ vaccination, and the impact on viral load setpoint during analytic treatment interruption (ATI) in people living with human immunodeficiency virus-1 (HIV-1, PLWH) who have initiated or will initiate antiretroviral therapy (ART) during acute HIV-1 infection (AHI).

Accelerated ART Initiation for PWHIV Who Are Out of Care

The main purpose of the study is to evaluate the effectiveness, of the ACCELERATE model of care to achieve HIV viral suppression at Week 24. The study will also assess the acceptability, appropriateness, feasibility, and sustainability of the ACCELERATE model of care. The ACCELERATE model combines a standardized method for outreach, the use of telehealth for rapid access to an HIV care provider, a simplified pre-approved HIV regimen, a free 30-day medication starter supply, and re-linkage to medical care.

Goals for Adherence with Low-cost Incentives

GOALS is a three-year randomized control trial (RCT) aimed at testing the effectiveness of three incentive designs to improve the ART adherence of those in need of adherence support. Participants in the first treatment group (T1, n=140) will be eligible for a prize drawing every three months if they reach the adherence target set for them by the study team, gradually increasing from their baseline adherence towards 90% by the end of the year. Participants in the second treatment group (T2, n=140) will be eligible if they reach the adherence target they set for themselves (subject to reaching 90% at the end of year 1 and each target being at least as high as the previous one). Participants in the third treatment group will have a fixed adherence target of 90% and will be eligible for a prize drawing every three months if this target is reached. All treatment groups will receive weekly motivational messages and a reminder of the upcoming prize drawing. The control group (T4, n=140) will receive the usual standard of care offered by the hospital and weekly motivational messages. Primary outcomes measured using Wisepill devices are mean ART adherence and the fraction of clients with adherence of 90% or more. Secondary outcomes are viral suppression, the fraction of clients with treatment interruptions of 48hrs or more, and retention in care.

Adenomyosis and Pregnancy Outcomes in Women Undergoing Assisted Reproductive Technology Treatment

Rationale: A rising number of adenomyosis cases are being diagnosed in women in the age group of 30 to 40 years. This is due to a combination of better diagnostic imaging techniques and a higher number of women delaying the fulfilment of their fertility aspirations. The association between adenomyosis and pregnancy outcomes in women with subfertility has not been adequately explained by existing evidence due to lack of data on the association between the severity of adenomyosis, disease location, presence of symptoms and coexisting gynaecological conditions and pregnancy loss in women undergoing fertility treatment. There is a need to improve our understanding of prognostic features which would be beneficial in counselling women with adenomyosis undergoing fertility treatment and inform future management options. The investigators propose a research body of work aimed at improving our understanding of adenomyosis and its association with pregnancy loss. Objective: The aim of the study is to determine the association between adenomyosis and pregnancy loss in women undergoing assisted reproductive technology (ART) treatment. Study design: Prospective multicentre cohort study. The cohort will comprise of women with adenomyosis undergoing ART treatment and the control group will include women with normal uterus on baseline ultrasound scan undergoing ART treatment during the study duration. Settings: The study will be conducted at all main CARE fertility units, one of the largest providers of fertility treatment in the United Kingdom. Participant population with exposure and sample size: The cohort group will comprise of women diagnosed with adenomyosis on pre-treatment baseline ultrasound scan before ART treatment who satisfy the eligibility criteria and consent to participate in the study. The total sample size for this study will be 750 participants with 375 women in each arm. Recruitment will take place over the course of 18 months. Diagnostic tool for detection of exposure: The diagnosis of adenomyosis will be made using transvaginal ultrasound scan (TVS) (2D and 3D Ultrasound and applying Morphological Uterus Sonographic Assessment (MUSA) criteria. Schematic mapping system of adenomyosis severity proposed by Lazzeri and colleagues will be used to grade the severity of adenomyosis. Eligibility: Inclusion criteria: All women aged \>18 years and ≤42 years undergoing IVF/ICSI cycle. Exclusion criteria: Women with coexisting fibroid uterus, endometrioma confirmed on USS or known laparoscopic diagnosis of endometriosis (with histological confirmation), untreated hydrosalpinx, uterine malformation, previous myomectomy, previous surgery for adenomyosis or inconclusive USS. Recruitment: All women undergoing pre-treatment pelvic ultrasound scans before ART treatment will be screened for adenomyosis at the participating centres. Women who meet the eligibility criteria will be provided with an information leaflet about the study. They will be enrolled in the study after informed consent is obtained. The severity of adenomyosis will be subsequently evaluated using stored 2D and 3D ultrasound scan (USS) images. Several demographic, clinical and treatment characteristics will be recorded for each participant. Control: To ensure adequate comparability of the cohort, women with normal uterus on baseline ultrasound scan during the study duration will be used as control and will be matched for the following variables: age, embryo quality, type of ART cycle (donor or self and IVF or ICSI) and number of embryos transferred. The eligibility criteria will be applicable to the controls as well. Outcome measures: Primary outcome: Pregnancy loss up to 24 weeks out of all pregnancies achieved. The pregnancy loss will include biochemical pregnancy loss, miscarriage, pregnancy of unknown location (PUL) and ectopic pregnancy. This will be reported per embryo transfer and per woman. Secondary outcomes:1. Implantation rate per embryo transfer (number of gestational sacs divided by number of embryos transferred) and per woman; 2. Biochemical pregnancy rate per embryo transfer (positive pregnancy test following embryo transfer) and per woman; 3. Clinical pregnancy rate per embryo transfer (presence of at least one intrauterine gestational sac on ultrasound) and per woman; 4. Ongoing pregnancy rate per woman (defined as a live pregnancy at 12 weeks onwards); 5. Live birth rate after 34 weeks per woman. Subgroup analysis: We will carry out subgroup analysis according to specific patient characteristics. These analyses will include, but not necessarily be limited to women with the following characteristics:1. Varying severity of adenomyosis; 2. Presence /absence of symptoms of adenomyosis; 3. Frozen vs. Fresh embryo transfer; 4. Short vs. long vs. ultralong ovarian stimulation protocol; 5. Recurrent miscarriages; 6. Other associations that may become apparent in post-hoc analyses.

Cardiometabolic Function in Offspring, Mother and Placenta After Assisted Reproductive Technology

The overall objective is to establish the first-of-its-kind longitudinal cohort of pregnant women, biological fathers/partners and offspring from pregnancies achieved by frozen embryo transfer (FET), fresh-embryo transfer (fresh ET) and naturally conceived (NC) to investigate maternal cardiometabolic profiles, fetal growth patterns and placental function during pregnancy as well as metabolic and endocrine health in the offspring. Additionally, the aim is to explore genetic and epigenetic patterns in placenta, fetus and parents. As secondary objectives, the investigator group will examine telomere length and minipuberty hormones in children born after FET, fresh-ET and NC.

Primary and Secondary Drug Resistance Mutations (DRMs) in HIV As a Risk Factor of Failure of ART, Including Two Drugs Based Regimens.

The presence of drug resistance mutations (DRMs) in HIV plays an important role in ART effectiveness. Despite very good results of ART, there is constant concern about the emergence of HIV strains with DRMs, what may lead to virological suppression failure. The concerns grow especially among patients treated with two drugs based regimens, including long acting therapies in injections (LAI ART) or regimens used in preexposure prophylaxis (PreP).

Ethanol Sclerotherapy Prior to ART

The goal of this randomized controlled trial is to assess the impact of ethanol sclerotherapy on ART cycle outcomes. The main questions it aims to answer are: 1. Does ethanol sclerotherapy before ART cycle has any impact on cumulative live birth rate in patients with endometrioma? 2. Does ethanol sclerotherapy improve chronic pelvic pain, dysmenorrhea, complications during oocyte retrieval, response to ovarian stimulation (number of mature oocytes retrieved), and pregnancy loss rates? Infertile patients with endometrioma between 4-10 cm who are scheduled for ART within 2 cycles will be randomized to ethanol sclerotherapy or no intervention.

The Impact of Endometrial Compaction on Assisted Reproductive Technology Outcome

Absence of endometrial compaction on the day of ET has adverse effects on success of ART outcome.

IVF Offspring Born in Guangzhou

The IVF Offspring Born in Guangzhou Cohort Study (IVF-BIG) was established to investigate the short- and long-term effects of exposure in early life on the health of mothers and offspring in Guangzhou, China. Data are collected regarding assisted reproductive technology (ART), environmental, occupational and lifestyle exposures as well as health outcomes in their later life. Biological samples including blood and tissue samples are also collected from participants.

Aspirin for the Prevention of Preeclampsia and Pregnancy Outcomes After Assisted Reproductive Technology

This study seeks to validate the hypothesis that nulliparous pregnant women after Assisted Reproductive Technology (ART) are at high risk of preeclampsia and perinatal complications and represent a subgroup for which aspirin prophylaxis during pregnancy may be effective in the prevention of preterm preeclampsia and other perinatal adverse outcomes.

The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in PLWH

Since the reasons for differential immune reconstitution in HIV-infected patients are still not fully understood, we considered it reasonable to investigate whether the presence of primary HIV drug resistance mutations could be one of the factors of inadequate immune reconstitution. Evaluation of unfavorable factors of immune reconstitution can help identify patients at risk of persistently low CD4 cell counts and CD4:CD8 ratios and requiring careful monitoring for progression to AIDS.