An interventional study of Intracytoplasmic Sperm Injection (ICSI) and Conventional Insemination (IVF) in Infertility, Female, Reproductive Techniques, Assisted and Fertilization in Vitro, sponsored by Shady Grove Fertility Reproductive Science Center. Recruiting at 1 site in United States. Open to female participants. Per ClinicalTrials.gov, last updated 2025-09-16.
Sponsored by Shady Grove Fertility Reproductive Science Center · Not applicable, Interventional, and Treatment
The goal of this clinical trial is to learn whether two different methods of helping eggs and sperm join-intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (IVF)-lead to better embryo development when using frozen donor sperm in people who do not have male fertility problems. The main questions it aims to answer are:
Does one method create more usable embryos (blastocysts) than the other?
Is there a difference in how often fertilization does not happen at all?
Do either of the methods lead to better embryo quality or early pregnancy?
Participants will:
Have their eggs divided into two groups. One group will be fertilized using ICSI (where a sperm is injected directly into an egg), and the other using conventional IVF (where eggs are mixed with sperm in a dish).
The fertilization method for each egg will be randomly assigned, with a random process also used to determine the assignment of any extra egg when an odd number is collected.
Continue regular fertility treatment while the study team compares the results of each fertilization method.
This study includes people with non-male factor infertility and uses frozen donor sperm. It hopes to learn whether ICSI, which is often used even when it may not be needed, truly helps improve outcomes compared to conventional IVF in these cases.
This is a prospective, randomized sibling-oocyte controlled trial designed to compare fertilization and embryo development outcomes between intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (IVF) using cryopreserved donor sperm in non-male factor infertility cycles. Despite widespread use of ICSI in assisted reproductive technology (ART), there is insufficient evidence supporting its routine use in non-male factor indications, especially in cycles utilizing frozen sperm where male factor infertility is not a contributing variable.
The study aims to address ongoing clinical debate and practice variation by evaluating whether ICSI offers meaningful advantages over conventional IVF in this specific context. Previous retrospective and meta-analytic data have suggested that while ICSI may reduce total fertilization failure (TFF), it may not improve-and may even negatively impact-other key clinical outcomes such as blastulation rate, embryo quality, and early pregnancy rates in non-male factor populations. Additionally, concerns about increased pregnancy-related complications with ICSI have been raised.
To reduce inter-patient variability and enhance internal validity, a sibling-oocyte design will be employed, allowing within-patient comparison of insemination methods. Oocytes retrieved from each participant will be randomized to either ICSI or conventional IVF. Randomization will be conducted prior to oocyte retrieval using computer-generated allocation. For patients with an even number of mature oocytes, half will be assigned to each insemination method. For those with an odd number, the extra oocyte will be randomly allocated according to the pre-specified scheme.
The fertilization process will begin shortly after oocyte retrieval. In the conventional IVF arm, mature oocytes will be inseminated using washed frozen-thawed donor sperm at a standard concentration and co-incubated for 16-18 hours. In the ICSI arm, a single motile sperm will be injected directly into each mature oocyte. All oocytes will undergo standard embryological assessment post-insemination, and embryos will be cultured under identical conditions.
The primary endpoint is the blastulation rate, defined as the number of usable blastocysts (meeting lab criteria for cryopreservation or transfer) per number of oocytes inseminated in each arm. Secondary outcomes include:
The study will enroll approximately 178 participants over 12 months at Shady Grove Fertility, where frozen donor sperm with normal post-thaw parameters is routinely available. Only non-male factor infertility patients using frozen donor sperm will be eligible, ensuring a controlled sperm quality baseline across study arms.
The hypothesis is that conventional IVF will demonstrate equivalent or superior blastulation rates compared to ICSI, with non-inferior fertilization outcomes and potentially better embryo morphology. Results from this trial will help refine clinical guidelines and may support a more evidence-based, resource-efficient use of ICSI.
IRB approval has been obtained, and informed consent will be secured from all participants. All procedures will adhere to Good Clinical Practice and applicable regulatory guidelines. Data confidentiality will be maintained throughout.
540 studies on the registry are indexed under Infertility, Female; 138 are open to participants now.
This study's planned enrollment of 95 is close to the median of 100 across 371 interventional studies indexed under Infertility, Female.
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Exclusion Criteria:
In this arm, a portion of each participant's mature oocytes will be inseminated using intracytoplasmic sperm injection (ICSI). A single frozen-thawed donor sperm cell will be injected directly into each oocyte using micromanipulation techniques. The oocyte assignment to ICSI will be determined through randomized sibling-oocyte allocation. Embryos will be cultured under standard laboratory conditions and assessed for fertilization (2PN), blastulation, embryo quality, and early clinical pregnancy outcomes.
Procedure: Intracytoplasmic Sperm Injection (ICSI)
In this arm, a portion of each participant's oocytes will be inseminated using the conventional in vitro fertilization (IVF) method. Frozen-thawed donor sperm with normal post-thaw parameters will be co-incubated with oocytes in culture media for fertilization. The oocyte assignment to this method will be determined through randomized sibling-oocyte allocation. Embryos will be cultured under the same laboratory conditions and assessed for fertilization (2PN), blastulation, embryo quality, and early clinical pregnancy outcomes.
Procedure: Conventional Insemination (IVF)
Mature oocytes are injected with a single frozen-thawed donor sperm cell using micromanipulation under a microscope. This fertilization method is performed shortly after oocyte retrieval. Sperm used are pre-screened and standardized for post-thaw motility and morphology. ICSI is conducted in accordance with standard embryology lab protocols. The oocyte allocation to ICSI is randomized within each participant's cycle.
Oocytes are inseminated by co-incubation with frozen-thawed donor sperm in a culture dish for 16-18 hours. Sperm are washed and prepared according to lab protocol to ensure motility and concentration suitability. This method does not involve direct sperm injection. Oocytes are randomly assigned to this method within each participant's retrieved cohort.
Blastulation Rate
The blastulation rate is defined as the number of "usable" blastocysts divided by the number of oocytes inseminated in each arm (ICSI and conventional IVF). A blastocyst is considered "usable" if it meets laboratory criteria for either cryopreservation or embryo transfer. Assessment is performed on Days 5-7 after fertilization using standard morphological grading under light microscopy.
Time frame: Day 5 to Day 7 post-insemination
Fertilization Rate
The fertilization rate is the number of oocytes that develop two pronuclei (2PN), indicating successful fertilization, divided by the total number of oocytes inseminated. Oocytes are assessed approximately 16-18 hours after insemination. A 2PN zygote is a marker of normal fertilization in IVF/ICSI cycles.
Time frame: Approximately 16-18 hours post-insemination
Total Fertilization Failure (TFF)
TFF is defined as the percentage of insemination arms (either ICSI or conventional IVF) within a cycle that result in zero fertilized oocytes (0% 2PN). This is assessed at the patient level. For example, if none of the oocytes in the conventional IVF group fertilize, that arm is considered to have experienced TFF.
Time frame: Approximately 16-18 hours post-insemination
Proportion of High-Quality Blastocysts
This outcome measures the proportion of blastocysts graded BB or higher on standard morphological grading scales. Embryos are assessed on Days 5-7 post-insemination. Blastocyst quality is determined based on expansion, inner cell mass, and trophectoderm appearance. Only embryos reaching the blastocyst stage are included in this metric.
Time frame: Day 5 to Day 7 post-insemination
Early Clinical Pregnancy Rate
Early clinical pregnancy is confirmed by the presence of a gestational sac visualized on transvaginal ultrasound, typically around 5-7 weeks after embryo transfer. The rate is calculated as the percentage of embryo transfer cycles in which at least one intrauterine pregnancy is confirmed.
Time frame: Approximately 5 to 7 weeks after embryo transfer
Plan to share: No
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