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.
Female patients undergoing IVF with frozen donor sperm at Shady Grove Fertility Center
Normal ovarian reserve (AMH > 1 ng/mL, AFC > 10)
Absence of male factor infertility
Post-wash parameters: >50% motility, >5mil concentration
Donor Sperm with significant male factor infertility (e.g., abnormal sperm concentration, motility, or morphology)
Any medical condition contraindicating ART
Crossover
Intracytoplasmic Sperm Injection (ICSI)
Procedure/SurgeryMature 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.
Conventional Insemination (IVF)
Procedure/SurgeryOocytes 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.
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.
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.
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.
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.
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