The maturity level of an egg (oocyte) at the time of retrieval directly influences its ability to be successfully fertilized and develop into a viable embryo. In assisted reproductive technologies (ART), this maturity is assessed by determining the stage of cell division the egg has reached, differentiating it into various grades, including the Metaphase I (M1) and Metaphase II (M2) stages. Understanding the distinctions between these two stages is necessary for laboratory procedures like in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). The ultimate goal is to identify and utilize the most developmentally competent eggs to maximize the chance of a successful pregnancy.
The Context of Oocyte Maturation
The life of an egg, or oocyte, is marked by meiosis, a unique process of cell division that reduces the chromosome number by half. This complex process is characterized by two distinct periods of meiotic arrest where the egg’s development pauses. The first and longest arrest occurs during the prophase I stage of meiosis, beginning before birth and lasting until puberty.
The resumption of meiosis is triggered by a surge of luteinizing hormone (LH) in a natural cycle or by a human chorionic gonadotropin (hCG) injection during a stimulated cycle for ART. This hormonal signal prompts the egg to complete Meiosis I, which is the transition point that separates M1 and M2 eggs. The M1 egg is in the middle of Meiosis I, while the M2 egg has completed this first division.
After Meiosis I is complete, the egg immediately enters Meiosis II, where it is arrested again at the metaphase II stage. This is the final stage of maturity, and the egg remains paused here until fertilization by a sperm occurs. Oocyte retrieval for ART is timed to capture the eggs after the completion of Meiosis I, ideally when they have reached this M2 stage of arrest. Eggs retrieved before the completion of Meiosis I are considered immature, specifically those at the M1 stage, and have not yet fully prepared their internal machinery for the fertilization process.
Defining Characteristics of M1 and M2 Eggs
The distinction between M1 and M2 eggs is made by embryologists in the laboratory based on clear visual and structural markers. These markers relate to the stage of meiotic division and the presence of a specific cellular byproduct called the polar body. The M1 stage, or Metaphase I, represents an egg that is still undergoing its first meiotic division.
A key physical characteristic of an M1 egg is the absence of the first polar body (PB1) outside the main cell membrane. The nuclear material inside the M1 egg is organized into a metaphase plate, but the nuclear envelope has broken down, so the nucleus is not visible as a distinct structure. Because the first meiotic division is not yet complete, the M1 egg still contains a diploid set of chromosomes.
In contrast, the M2 stage, or Metaphase II, indicates a fully mature egg that has completed the first meiotic division. The most defining visual marker of an M2 egg is the visible presence of the first polar body, which is a small, extruded sac of genetic material located just under the egg’s outer layer.
The extrusion of this polar body signifies that the egg has successfully shed half of its chromosomes to achieve a haploid state, which is necessary for fertilization. The M2 egg is arrested in this state and is structurally and genetically ready for the fusion with a sperm. Therefore, the presence of the first polar body is the simple, non-invasive indicator that the egg has achieved full competence for fertilization.
Utility in Assisted Reproductive Technology
The maturity of an egg, specifically its M1 or M2 status, dictates how it is handled and utilized in ART procedures. The M2 egg is considered the only stage immediately competent for fertilization because it has completed the complex Meiosis I division. For both conventional IVF and ICSI, only M2 eggs are selected for insemination shortly after retrieval and denudation.
The M1 egg, being immature, is not immediately ready for sperm injection due to its incomplete nuclear maturation. If an M1 egg were fertilized, it would likely result in an abnormal embryo with an incorrect number of chromosomes. These M1 eggs are not discarded but are often placed in a culture dish in the laboratory for a process called In Vitro Maturation (IVM).
IVM allows the M1 egg to continue its development outside the body, with the hope that it will transition to the M2 stage. Studies show that M1 eggs that mature in the lab may have lower fertilization rates and blastocyst conversion rates compared to eggs that were M2 at the time of retrieval. Despite the lower success rates with lab-matured M1 eggs, their maturation and subsequent use can be a valuable strategy to increase the total number of usable eggs in a cycle, particularly for patients with a low egg yield.