Empty Follicle Syndrome During IVF: Why Does It Happen?

Empty follicle syndrome — sounds pretty suspicious, right?

But what does it mean if you're going through IVF?

How can follicles even be empty?

And if there's no egg, how can fertilization happen?

As rare as it is, this empty follicle syndrome is a condition that's often treatable, but might require an alternative fertility treatment.

So how exactly do we go about this rare syndrome, and what are some treatment options?

Let's find out.

In this article: 📝

What is empty follicle syndrome?

Empty follicle syndrome is a rare genetic condition where a follicle shows apparent signs of normal growth and development but may not contain an egg, or have an egg inside that underwent early death.

This can hinder fertility, too — here's the "ideal" situation with follicles when trying to conceive:

Follicle with egg inside ➡️ Egg grows and develops to maturity ➡️ Egg gets fertilized by sperm

But, with empty follicle syndrome, there's a roadblock at the second stage, and the egg doesn't make it to maturity.

What are the symptoms of empty follicle syndrome?

Here's the tricky part— empty follicle syndrome can have little to no symptoms that can help detect it earlier than the egg retrieval stage.

This is because, in the ultrasound, the growing follicles seem normal.

But there are some other things you can ask your doctor about if you're worried about empty follicle syndrome:

• Revisit your medical history and check for instances in previous IVF cycles
• Check your trigger shot dosage in previous IVF cycles
• Check hormonal levels on the day of egg retrieval, which could indicate pre-maturation of eggs
• Look for any previous instances of empty follicle syndrome in your family history

How do I know if my follicle contains eggs?

An ultrasound is the standard way to check follicle growth and development.

During a typical menstrual cycle, there are some follicles selected to grow that month.

Their growth is measured on the ultrasound, as they range from immature sizes (4mm) to mature follicle sizes of 18-25mm.

Smaller follicles are expected to have immature eggs, or no eggs at all, and bigger follicles are often expected to grow and release mature eggs.

What causes empty follicle syndrome?

The primary cause behind empty follicle syndrome depends on whether it's a false or a true syndrome.

But what's the difference between false and true empty follicle syndrome?

False empty follicle syndrome

A false empty follicle syndrome can happen during an IVF cycle.

During a cycle, the final trigger shot to mature the egg is given 36 hours before the egg retrieval.

But, for false EFS to occur, the final trigger shot (hCG) for maturing the egg is given later than the decided duration for that cycle.

In this case, the egg and its surrounding cells fail to detach from the follicle.

During the egg retrieval, the eggs fail to be aspirated due to this reason.

Some other, more uncommon reasons for this condition include:

• Incomplete aspiration of eggs
• Facing technical issues with the machine during egg retrieval.
• Premature rupture and release of eggs before the retrieval, due to hormonal reasons. In this case, some eggs may or may not be retrieved.

True empty follicle syndrome

On the other hand, a true empty follicle syndrome is a rare genetic condition where no eggs are retrieved in an IVF cycle.

While there's no exact reason behind this, some studies have suggested a few, like:

• Due to the deletion of a chromosome or genetic material
• Very low ovarian reserve and ovarian aging
• Early egg death due to defective gene expression of supportive cells

In true empty follicle syndrome, the outcome is the same — a lack of eggs during an egg retrieval.

But the reasons can vary widely — while a false condition is preventable, a true empty follicle syndrome requires alternatives as treatment.

Can PCOS cause empty follicles?

We don't think so — there are no studies that link PCOS with empty follicles.

So if you're worried that PCOS could mean that you have empty follicle syndrome, rest assured that there's no link right now.

Can endometriosis cause empty follicles?

Potentially, yes — endometriosis can be a risk factor for empty follicle syndrome, according to this study.

This can happen when the endometrial cyst has penetrated or affected the ovary, leading to a disturbance in the normal growth and development of the follicles that house the eggs.

Is it common to have empty follicles?

It's actually quite uncommon to have empty follicles during an egg retrieval.

In fact, some studies estimate the occurrence of empty follicles in only 0.2-0.7% of cases.

What happens to follicles that don't ovulate?

Follicles that don't ovulate or release eggs, either undergo cell death or might get filled with fluid and turn into a cyst.

But there are no serious effects of such cysts as they are 1-3 cm in size and typically go away on their own after a few months.

Can empty follicles be penetrated by sperm?

In short, no — this is because empty follicles don't have eggs for sperm to penetrate to cause fertilization.

And sperm penetrate mature eggs in the fallopian tube, which are already released from the follicle, which is left behind in the ovaries.

Can empty follicle syndrome be treated?

Yes, empty follicle syndrome can be treated if it's a false empty follicle syndrome.

But a genetic cause for empty follicle syndrome requires an alternative (if you're trying to conceive), like donor eggs.

How to prevent empty follicle syndrome

Currently, there is no way to prevent true empty follicle syndrome.

But, if it's a case of false empty follicle syndrome caused by variation in your IVF trigger shot, pre-maturation of eggs, or errors during egg retrieval, it can be prevented and resolved by your healthcare provider.

How do you overcome empty follicle syndrome?

You and your doctor can work together to overcome empty follicle syndrome during an IVF cycle.

Here are some ways that patients and healthcare professionals can play their part:

What you can do:

• Be honest and clear about your family and medical history, especially if there's any history of empty follicle syndrome.

What your healthcare provider can do:

• Explore strategies like dual-trigger to improve outcomes in borderline empty follicle syndrome.
• Ensure that the trigger shot is provided at the right time, not any later.
• Avoid delaying egg retrievals.
• Ensure that all the equipment used for egg retrievals is error-free.
• Explain and provide alternatives for true empty follicle syndrome, like using donor eggs.

It can be challenging to navigate something like empty follicle syndrome, especially since it's relatively rare — your healthcare provider might be experiencing for the first time, too.

But there's always another path or an alternative fertility treatment that's right for you — no two cycles are alike, and no two cases of empty follicle syndrome are the same.

Throughout your TTC journey, there's a whole community of women who get it, just join us on Peanut.