In the fast-paced world of reproductive endocrinology and infertility (REI), even seasoned clinicians from other specialties can find themselves lost in the weeds of embryo reports. While most of us recall the basics of mitosis and meiosis from medical school, the clinical nuances of embryo morphology and grading are often not taught until fellowship.

Understanding these metrics is essential for informed decision-making. Whether you are an OB/GYN managing patient expectations or a clinician undergoing IVF yourself, here is a practical, evidence-based overview of embryo grading.

The early stages: days 0 to 3

When eggs are retrieved during an ultrasound-guided transvaginal retrieval (Day 0), the laboratory works with a defined number of oocytes. These eggs are either exposed to sperm (standard insemination) or injected with a single sperm (intracytoplasmic sperm injection, or ICSI). A fertilization check is performed approximately 18 hours later.

By Day 1, the goal is to see an embryo with two pronuclei (one maternal and one paternal), known as a 2PN embryo. Variations can include immature eggs or embryos with 0PN, 1PN, or 3PN or greater. Because each pronucleus contains a haploid set of chromosomes, deviations from 2PN raise concern for abnormal ploidy. However, because fertilization timing can be missed, embryos are often kept in culture to assess subsequent development.

By Day 3, embryos should have undergone exponential division, ideally reaching the eight-cell stage. Day 3 grading includes a number and a letter. The number reflects cell count (e.g., 6, 8, or 10 cells). Even numbers generally correlate with better outcomes, although odd-numbered embryos can and do result in live births. The letter reflects morphology: “A” or “B” grades indicate minimal fragmentation and cohesive blastomeres, while “C” or “D” grades suggest poorer morphology.

Between Days 3 and 5, embryos transition through the morula stage (a compact ball of cells that is difficult to grade). As a result, most laboratories do not formally assess embryos on Day 4.

Understanding blastocyst grading

By Day 5 or 6, embryos ideally reach the blastocyst stage, characterized by a fluid-filled cavity (the blastocele), the inner cell mass (ICM), and the trophectoderm (TE). Some labs extend culture to Day 7, but implantation rates are generally lower due to delayed development.

Blastocyst grading uses one number and two letters (e.g., 4AA). The number reflects the degree of expansion and hatching from the zona pellucida, not cell count. Grades 1 and 2 represent early blastocysts with less distinct ICM and TE layers. Grade 3 is a full blastocyst with clearly defined layers. Grade 4 indicates an expanded blastocyst with thinning zona pellucida. Grade 5 describes an actively hatching embryo, and Grade 6 a fully hatched embryo. Importantly, a Grade 6 embryo is not inherently “better” than a Grade 4; what matters is viability, expansion, and developmental momentum. When counseling patients, I often describe this stage as the embryo actively “looking for a home.”

The first letter grades the ICM (the cluster of cells that will become the fetus), while the second letter grades the TE, which forms the placenta. As with most grading systems, A is superior to B, which is superior to C. The TE grade is clinically significant, as these cells mediate implantation and early nutrient exchange.

Debate persists regarding the relative importance of ICM versus TE grade and whether Day 5 embryos are superior to Day 6 embryos. Individual laboratories maintain their own outcome data, but to date, no definitive conclusions have settled these questions.

Beyond morphology: genetic testing

While morphology helps prioritize embryos for transfer, it does not tell the full story. A high-quality embryo can be aneuploid, and a lower-graded embryo can result in a healthy, euploid live birth.

Many laboratories now offer Preimplantation Genetic Testing for Aneuploidy (PGT-A), which involves biopsying several trophectoderm cells at the blastocyst stage. At this point, embryos contain approximately 100–200 cells. Although PGT-A is widely used, its benefit remains nuanced. Data suggest that in patients under 38 without recurrent pregnancy loss, PGT-A may not improve outcomes and may even be detrimental due to additional embryo manipulation. In contrast, for patients over 38 or those with recurrent aneuploid losses, PGT-A can improve pregnancy rates per transfer, reduce miscarriage risk, lower twin rates with single embryo transfer, and shorten time to live birth.

However, growing awareness of mosaicism and variability among testing platforms has tempered early enthusiasm. Interpreting mosaic, segmental, or “no result” embryos is complex and best done in collaboration with an experienced genetic counselor.

Decisions about PGT-A should be individualized and made in consultation with a reproductive endocrinologist before embryos are frozen. Evidence suggests that embryos subjected to thawing, biopsy, and refreezing have lower success rates than those frozen and thawed only once.

Clinical takeaways

Embryo grading blends objective science with subjective expertise. While grades help prioritize transfer order (favoring, for example, a 4AA over a 3CC) it is critical to remember that “fair” or “poorly” graded embryos still lead to healthy live births. In some cases, personal considerations, including sex preference, may also influence transfer sequencing.

As physicians, our role is to demystify this process for patients. We work alongside skilled embryologists, trusting their daily expertise while helping patients contextualize uncertainty in a process that often feels anything but predictable.

Erica Bove is a double board-certified obstetrician-gynecologist and reproductive endocrinology and infertility (REI) specialist at the University of Vermont Medical Center, where she also directs the REI fellowship program. She is the founder and CEO of Love and Science: Thriving Through Infertility, a platform dedicated to guiding individuals and couples through the challenges of fertility with evidence-based medicine, coaching, and community.

Dr. Bove is passionate about supporting women physicians in building their families with confidence and compassion, blending science with intuitive, whole-person care. She extends her work beyond the clinic through her podcast and outreach on LinkedIn, Instagram, and Facebook.

Her academic contributions include studies on physician wellness and burnout, fertility preservation in oncology patients, and reproductive outcomes in complex medical contexts, with publications in Obstetrics and Gynecology, Journal of Graduate Medical Education, Endocrinology, and American Journal of Clinical Oncology.

Through clinical care, teaching, and advocacy, Dr. Bove is committed to advancing reproductive medicine, supporting healers, and creating a legacy of connection, empowerment, and compassion.