Why Do Embryos Arrest Between Day 3 and Day 5?

Evidence-based · Written by Dr. Lejla Fazlicic, D.Ac, L.Ac · All key claims cited to peer-reviewed research

And the number almost nobody gives you: in the largest study of its kind, most embryos do not make it. That is not a failed cycle. That is the normal arithmetic of IVF, and understanding it changes what your result means.

Working out what your particular cycle is telling you — and what is worth investigating before the next one — is the hard part to do alone.

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Before anything else: if you have spent the days since that call rereading the embryology report and looking for the thing you did wrong, put it down. Nothing in this literature identifies a behaviour that decides whether an embryo compacts. The internet will tell you Day 3 arrest is the egg and Day 5 arrest is the sperm. That division is not supported, and it has caused a great deal of unnecessary blame in both directions.

What actually happens between Day 3 and Day 5?

Embryologists track development against a rough schedule. Real embryos vary, and the variation itself is informative rather than alarming.

Typical developmental milestones by day after fertilisation — a guide, not a standard your embryos are being graded against

Day	What is usually seen
Day 1	Fertilisation check. A normally fertilised embryo typically shows two pronuclei
Day 2	Early cleavage divisions, usually a few cells
Day 3	Often around 6–8 cells, with real variation either side
Day 4	Compaction into a morula — cells pull together and the outlines blur
Day 5–6	Blastocyst: a fluid cavity, an inner cell mass, and a trophectoderm

The reason this window is difficult is a handover. For the first few divisions the embryo runs almost entirely on supplies packed into the egg before ovulation — RNA, proteins, mitochondria, energy stores. Then it has to clear those maternal instructions and start directing development from its own genome. That handover is called the maternal-to-zygotic transition, and it happens right around the cleavage stage this article is about.

In the largest molecular study of arrested human embryos, the researchers found the arrested ones had entered what they described as a senescent-like state — cell cycle stalled, ribosomes and histones switched down. They could sort them into three types: embryos that never completed the maternal-to-zygotic transition, and two groups with low glycolysis and either high or low oxidative phosphorylation (Yang et al., 2022).

So an embryo can look entirely reasonable on Day 3 and still not have what the next 48 hours require. A good Day 3 is a checkpoint passed, not a prediction.

Is it normal for most embryos not to make blastocyst?

Yes — and this is the single most useful thing on this page, because almost nobody is told it before the phone call.

In the study above, around 60% of IVF embryos arrested before compaction. Note the exact window there: that figure describes arrest at the 3-to-8-cell stage, slightly earlier than Day 3-to-Day 5, so treat it as the scale of the problem rather than the precise rate for your window. A 2024 review puts early embryonic arrest at something affecting 40% of patients in treatment (Zhang et al., 2024).

The more useful way to hold it is per egg. In a series of 28,959 fresh mature eggs from 2,031 patients, the mean number of mature eggs needed to produce one blastocyst rose steadily with age:

Mean mature (MII) eggs used per blastocyst, fresh cycles — Murugappan et al., 2025

Age at retrieval	Mature eggs per blastocyst
18–34	2.2
34–37	2.5
38–40	2.9
41–42	3.9

Read that table against your own cycle before you read anything into it (Murugappan et al., 2025). If you were 39 with six mature eggs, the arithmetic predicts about two blastocysts — so one or three is not a signal of anything. These are means from large numbers, and a single retrieval is a very small sample. With a small cohort, chance alone moves the final number a long way.

Does arrest mean the embryos were chromosomally abnormal?

Not reliably, and this is where the most damage gets done in the retelling.

Chromosomal abnormality — aneuploidy — is a genuine and important cause of embryos failing to develop, and it becomes more common as egg age rises. That much is not in dispute. What does not follow is the inference most people are left with: that an arrested cohort was therefore a genetically abnormal cohort.

The cleanest test of this is small but pointed. Thirty Day-3 embryos, all from couples having preimplantation genetic testing, all of good quality, were cultured on and then analysed by whole genome amplification. Eighteen (60%) arrested; twelve (40%) became blastocysts. Nineteen of the thirty (63.3%) were euploid — and the euploid embryos were split almost evenly between the two groups: 12 of the arrested embryos and 7 of the blastocysts. The difference was not statistically significant (Orvieto et al., 2022).

Thirty embryos is not a large study and I would not build a clinical decision on it. But it does what it set out to do: it shows that chromosome number alone did not separate the embryos that made it from the ones that did not. Euploid embryos arrest. Aneuploid embryos sometimes reach blastocyst.

The practical consequence: a cycle with poor blastocyst development is a reason to discuss egg age and embryo chromosome risk with your physician. It is not evidence that every embryo was abnormal, and nobody can tell you that it was.

Was it the egg or the sperm?

Most likely neither, as a clean answer — and the question itself is built on a split the evidence does not support.

The version circulating online is that arrest before Day 3 is an egg problem and arrest after Day 3 is a sperm problem, on the logic that the paternal genome only starts mattering once the embryo runs on its own DNA. The biology behind that is real. The diagnostic rule built on top of it is not.

What the egg supplies is the entire operating environment for the first days: mitochondria and energy reserves, maternal RNA and protein, the spindle machinery for accurate chromosome separation, and the DNA repair capacity that acts on the paternal genome after fertilisation. Reduced oocyte competence can show up as trouble with chromosome segregation, energy production, clearing maternal messages, compaction, or blastocyst formation. Age influences this, but it is a continuum — younger patients have cycles where embryos arrest, and people in their late thirties and forties produce blastocysts that become healthy babies.

What the sperm supplies is the paternal genome plus factors involved in fertilisation and early development. A standard semen analysis measures concentration, motility and morphology; it does not measure DNA integrity. Sperm DNA fragmentation has been associated in some studies with poorer embryo development and lower blastocyst formation, and it is biologically plausible that the effect would surface once the embryo is replicating and relying on paternal DNA. But the evidence is heterogeneous, the assays differ between laboratories, and no study lets you read backwards from an arrest pattern to a sperm cause. The egg also repairs some sperm DNA damage — how much appears to depend on both the oocyte and the amount of damage.

The systematic review that mapped this whole field across 76 studies found arrest associated with embryonic factors (gene variants, mitochondrial DNA copy number, methylation patterns, chromosomal abnormalities, metabolic profile, morphology) and parental factors, rather than resolving to one side (Sfakianoudis et al., 2021). If you want the male side worked through properly, it is in his 50%: male factors in embryo quality and sperm DNA fragmentation and IVF failure.

Could it be the embryo's metabolism?

Possibly, and this is the most interesting research of the last few years — with a caveat you should hear before you go looking.

Compaction and blastocyst formation are expensive. Cells divide, communicate, pump fluid, repair DNA and differentiate, all at once. The molecular work on arrested human embryos found disrupted metabolic pathways, stalled cell cycles, altered mitochondrial activity and abnormal epigenetic regulation — which is the best current explanation for why a chromosomally normal embryo can still stop (Yang et al., 2022).

Here is the caveat, and I would rather you hear it from me than find it yourself and wonder why I left it out. That same study found that treating the arrested embryos with resveratrol or nicotinamide riboside partially rescued the arrested phenotype. That is embryos in a dish, treated in a laboratory, in an experiment designed to test a mechanism. It is not a person taking a supplement for three months, and nobody has shown that taking either one improves blastocyst rates in an IVF cycle. If you see that finding used to sell you something, that is the gap it is being used to jump.

Is a slow embryo the same as an arrested embryo?

No, and the distinction is worth understanding before you accept a final count.

The systematic review defines developmental arrest as a lack of cell division for at least 24 hours. That threshold is a working definition, not a verdict — some embryos pause and resume, and some simply run late. Plenty form blastocysts on Day 6 rather than Day 5, and some laboratories culture to Day 7.

Day 6 blastocysts do perform less well on average. In a study of single frozen euploid transfers, Day 5 blastocysts gave higher implantation (68.8% versus 48.3%) and live birth (63.7% versus 40.4%) than Day 6, with the gap widest in older patients and in lower-quality embryos. The authors' own conclusion, though, is the part that matters to you: Day 6 euploid transfer still yields acceptable implantation and pregnancy rates (Lang et al., 2025).

So "slower" is a reason to set expectations, not to write an embryo off. It is a fair question to ask your clinic whether embryos were cultured through Day 6, and Day 7 where that is their practice.

Could it have been the laboratory?

Possible, unlikely in a single cycle, and worth asking about if it repeats.

Embryos are grown outside the body, so temperature, pH, oxygen, culture media, light and handling time all matter, and good laboratories run validated systems and quality control to hold those steady. But be careful how much weight you put on any one lab variable, because the evidence is thinner than the confidence with which it gets stated.

Low-oxygen culture is the clearest example. It is widely recommended, and the meta-analysis of 21 studies found low oxygen better for live birth or ongoing pregnancy at a relative risk of 1.1 (95% confidence interval 1.0 to 1.3) — but the authors graded that as very low quality evidence and concluded that clinical equipoise remains (Nastri et al., 2016). A roughly 5% difference, uncertain. That is worth knowing in both directions: it is not a strong argument that a lab using atmospheric oxygen cost you your cycle, and it is not a strong argument that low oxygen would have saved it.

Arrest is common enough to occur in excellent programs. If a pattern repeats across cycles, reasonable questions are how the clinic reviews its own blastocyst conversion data, what it expects for a cohort like yours, and whether anything unusual was noted during the culture period.

What the evidence does not show

This is the part most pages skip, and naming the gaps is what makes the rest of the page trustworthy:

• That the day an embryo stops identifies the cause. No study supports reading a specific cause from timing alone.
• That arrest proves aneuploidy. In the one study that tested it directly, euploid embryos were split between the arrested and the blastocyst groups with no significant difference.
• That any supplement, diet or protocol prevents embryo arrest. The resveratrol finding is embryos in culture, not patients taking capsules.
• That morphology predicts which individual embryo will make blastocyst. ASRM notes Day 3 cell number and fragmentation are associated with blastocyst potential while reliable individual-embryo markers remain limited (ASRM Practice Committee, 2018).
• That one cycle predicts the next. Each retrieval yields a different cohort of eggs, and with small numbers chance moves the result substantially.
• That the maternal-effect genes explain most cases. Rare variants in genes expressed in the egg can contribute to repeated early arrest, but these are specialist situations relevant to a striking pattern across multiple cycles — not to one disappointing result.

What we do with this

1. Get the full cycle numbers, not the final one. Eggs retrieved, mature, normally fertilised, still dividing on Day 3, and compacting on Day 4. The shape of the drop-off is more informative than the blastocyst count.
2. Compare against the arithmetic before you interpret. Roughly 2.2 mature eggs per blastocyst under 34, rising to 3.9 at 41–42. Work out what your cohort predicted.
3. Ask whether embryos were slow or definitively arrested, and whether culture continued to Day 6 or Day 7.
4. Ask about the fertilisation method. Whether conventional IVF or ICSI was used, and whether there is a reason to reconsider for the next cycle.
5. Consider a male-factor review if the pattern repeats — repeat semen analysis, a reproductive urologist, and selective DNA fragmentation testing where the clinical picture supports it. Not as blame; as one of the few remaining places to look.
6. Wait for a pattern before drawing conclusions. One cohort is one sample. Recurring patterns across cycles are what justify specialist evaluation or genetic counselling.

The day your embryos stopped is a clue about which part of a very demanding transition was under strain. It is not a verdict on your eggs, his sperm, your clinic, or your next cycle — and anyone who tells you otherwise from a Day 5 report is telling you more than the evidence allows.

Related reading

• Why did my IVF fail when everything looked normal?
• Was the failed cycle my fault?
• Egg quality in the 90 days before retrieval
• His 50%: male factors in embryo quality
• Sperm DNA fragmentation and IVF failure
• Sperm DNA fragmentation test: cost and results
• What nobody can tell you yet about preparing for IVF
• The research library

Frequently asked questions

Why do embryos arrest between Day 3 and Day 5?

Because this window contains the hardest transition in early development. The embryo must stop running on supplies stored in the egg and start directing development from its own genome, generate enough energy to keep dividing, compact into a morula, and begin forming a blastocyst. Chromosomal abnormalities, reduced egg competence, sperm DNA integrity, disrupted metabolism and — less often — culture conditions can all contribute. The timing of arrest is a clue about which processes were under strain, not a diagnosis of one cause.

Is it normal for no embryos to make it to blastocyst?

It is more common than most people are told. In one molecular study, around 60% of IVF embryos arrested before compaction, and a 2024 review describes early embryonic arrest as affecting about 40% of patients in treatment. In a series of 28,959 fresh mature eggs, the mean number of mature eggs needed per blastocyst was 2.2 at ages 18–34, rising to 3.9 at ages 41–42. With a small cohort, chance alone moves the final number substantially, so one disappointing cycle is a small sample rather than a verdict.

Does embryo arrest mean the embryos were genetically abnormal?

Not reliably. Aneuploidy is a genuine cause of embryos failing to develop and becomes more common with egg age, but arrest does not prove it. In a study of thirty good-quality Day 3 embryos cultured on and analysed genetically, eighteen arrested and twelve became blastocysts — and of the nineteen that were euploid, twelve were among the arrested group and seven among the blastocysts, a difference that was not statistically significant. Euploid embryos arrest, and some aneuploid embryos reach blastocyst.

Is Day 3 to Day 5 arrest an egg problem or a sperm problem?

Usually neither as a clean answer. The claim that arrest before Day 3 means the egg and after Day 3 means the sperm is not supported by evidence. The egg supplies the mitochondria, energy reserves, maternal RNA, spindle machinery and DNA repair capacity that carry the first days; the sperm supplies the paternal genome and factors involved in fertilisation. A systematic review of 76 studies found arrest associated with both embryonic and parental factors rather than resolving to one partner.

Can a slow-growing embryo still become a healthy baby?

Yes. Developmental arrest is defined in the research as a lack of cell division for at least 24 hours, but some embryos pause and resume, and many form blastocysts on Day 6 rather than Day 5. Day 6 euploid blastocysts do perform less well on average than Day 5 — implantation 48.3% versus 68.8% and live birth 40.4% versus 63.7% in one study of single frozen transfers — but the authors concluded that Day 6 transfer still yields acceptable pregnancy outcomes. It is worth asking whether your clinic cultures to Day 6 and Day 7.

Can supplements or lifestyle changes prevent embryo arrest?

No supplement, diet or protocol has been shown to prevent embryo arrest. The research finding sometimes used to suggest otherwise is that resveratrol and nicotinamide riboside partially rescued arrested embryos in laboratory culture — embryos in a dish, in a mechanism experiment, not people taking capsules before a cycle. Embryo metabolism is a genuinely promising research area, but there is currently no validated intervention, and claims that there is should be treated with caution.

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This article is educational and reflects associations reported in the scientific literature. It is not medical advice, not a diagnosis, and not a way to interpret your own embryology report. As a Doctor of Acupuncture I offer lifestyle guidance that works alongside your physician and fertility clinic — I do not diagnose, interpret laboratory results, or prescribe. Decisions about testing, fertilisation method and treatment belong with your reproductive endocrinologist and embryology team.

References

1. Yang Y, Shi L, Fu X, et al. Metabolic and epigenetic dysfunctions underlie the arrest of in vitro fertilized human embryos in a senescent-like state. PLoS Biology. 2022;20(6):e3001682. PMID 35771762
2. Orvieto R, Jonish-Grossman A, Maydan SA, Noach-Hirsh M, Dratviman-Storobinsky O, Aizer A. Cleavage-stage human embryo arrest, is it embryo genetic composition or others? Reproductive Biology and Endocrinology. 2022;20(1):52. PMID 35300691
3. Sfakianoudis K, Maziotis E, Karantzali E, et al. Molecular drivers of developmental arrest in the human preimplantation embryo: a systematic review and critical analysis leading to mapping future research. International Journal of Molecular Sciences. 2021;22(15):8353. PMID 34361119
4. Zhang J, Lv J, Qin J, et al. Unravelling the mysteries of early embryonic arrest: genetic factors and molecular mechanisms. Journal of Assisted Reproduction and Genetics. 2024;41(12):3301–3316. PMID 39325344
5. Murugappan G, et al. Clinical utilization and outcomes over eight consecutive years following oocyte cryopreservation. Journal of Assisted Reproduction and Genetics. 2025;42(2):413–421. PMID 39633145
6. Lang J, Hong Y, Yang X, et al. Delayed blastulation and pregnancy outcomes in single frozen-thawed euploid blastocyst transfer. Frontiers in Endocrinology. 2025;16:1686274. PMID 41427036
7. Nastri CO, Nóbrega BN, Teixeira DM, et al. Low versus atmospheric oxygen tension for embryo culture in assisted reproduction: a systematic review and meta-analysis. Fertility and Sterility. 2016;106(1):95–104.e17. PMID 27012651
8. Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Assisted Reproductive Technology. Blastocyst culture and transfer in clinically assisted reproduction: a committee opinion. Fertility and Sterility. 2018;110(7):1246–1252. PMID 30503113