Karyotype Testing for Unexplained Infertility: What You Need to Know

In early November of 2025, I met a couple whose story perfectly captures why I do what I do.

They’ve been trying to conceive since their mid-20s. They did everything right: started with medicated IUIs, moved to IVF, and over several years, went through six IVF cycles at multiple well-known fertility clinics. Each time, the result was the same: disappointment.

The female partner had polycystic ovary syndrome (PCOS), so while her egg retrievals yielded many eggs, a large proportion were immature. The few that did fertilize often failed to develop into blastocysts or came back genetically abnormal after testing. Despite being young, healthy, and diligent, every attempt ended with the same devastating outcome.

At their last clinic, they were told something that made their hearts sink:

“This is just bad luck. You might need to move on to donor eggs.”

But something didn’t sit right. They couldn’t shake the feeling that there had to be an explanation.

So they kept searching, and one day, after watching one of my videos about why some patients have a low conversion rate from eggs to embryos, they scheduled a consult. During our meeting, I asked a question no one had before:

“Have you had a karyotype test done?”

They hadn’t. And that simple oversight, after six IVF cycles, and three different clinics, turned out to be the missing piece of their puzzle.

When we ran the test, the answer was clear: the male partner carried a translocation, a rearrangement of chromosomes where a piece of one chromosome had broken off and attached to another.

He was perfectly healthy. But that subtle structural rearrangement meant that many of the embryos they created were chromosomally unbalanced, meaning they either carried too much or too little genetic material to develop normally.

For years, their struggle had been written off as “bad luck.” But now, there was finally a biological explanation, all thanks to this powerful, but often overlooked, genetic testing tool called ‘karyotype testing’.

My name is Dr. Lucky Sekhon, and I am a double board-certified Reproductive Endocrinologist and Infertility (REI) specialist. Through this blog, my Instagram account and my upcoming book “The Lucky Egg: Understanding Your Fertility and How to Get Pregnant Now”, my goal is to help declutter the myriad of conflicting advice online to give you scientifically backed information about fertility and what it takes to get pregnant. In this blog post, I will explore what karyotype testing is, and how it could be a very powerful tool in diagnosing unexplained infertility.

What Is a Karyotype Test?

A karyotype test is a simple blood test that examines the number and structure of your chromosomes. Humans typically have 46 chromosomes, arranged in 23 pairs. A karyotype organizes these under a microscope so we can look for missing, extra, or rearranged pieces of DNA.

It’s one of the most basic genetic tests in medicine, yet it’s often overlooked in fertility workups.

In this case, that single test explained years of failed cycles and emotional suffering.

Studies have shown that structural chromosomal rearrangements, such as translocations, are present in roughly 2–5% of couples experiencing recurrent miscarriage or repeated IVF failure (Franssen et al., Fertility and Sterility, 2005; ASRM Practice Committee, 2023). Identifying them early can dramatically change how we approach treatment.

Understanding Translocations: When Chromosomes Swap Places

A translocation happens when parts of chromosomes break off and attach to other chromosomes.

There are two main types:

Type	What Happens	Effect on Fertility
Reciprocal Translocation	Two chromosomes exchange fragments	Can cause embryos with missing or extra genetic material
Robertsonian Translocation	Two chromosomes (usually 13, 14, 15, 21, or 22) fuse together	Can cause a high rate of chromosomally unbalanced embryos

The patient’s partner had a Robertsonian translocation, one of the most common structural rearrangements. People who carry this type of translocation are typically healthy because they have all the right genetic information: it’s just rearranged.But during fertilization, chromosomes need to divide evenly. When they’re fused, they can’t always separate correctly, and this leads to imbalanced embryos, embryos that rarely implant or result in miscarriage.

When Should You Consider Karyotype Testing?

You don’t need to go through six rounds of IVF to justify this test. In fact, karyotype testing should be considered much earlier if you have:

• Two or more miscarriages
• Repeated failed IVF cycles despite normal embryos
• A low blastocyst or fertilization rate for your age
• A family history of chromosomal abnormalities
• Unexplained infertility after normal initial testing

It’s shocking how many couples endure years of treatment without anyone ordering this simple test. No one should go through six rounds of IVF and multiple clinics before someone thinks to run a basic genetic test.

How It Changes Treatment

When a Robertsonian translocation or other chromosomal rearrangement is found, it doesn’t mean pregnancy is impossible, it simply means we need to change the strategy.

Couples in this situation can still create embryos together, but the odds of making a chromosomally normal embryo are lower. That’s why we often pivot to IVF with preimplantation genetic testing for structural rearrangements (PGT-SR).

This approach allows us to identify embryos with the correct chromosomal balance before transfer. It can reduce miscarriage risk and improve live birth rates in carriers of balanced translocations (Sun, L., Tao, X., Gu, J., et al. “Preimplantation genetic testing for couples with balanced chromosomal rearrangements: clinical outcomes and characteristics.” Reproductive Biology and Endocrinology, vol. 22, no. 1, 2024, p. 41. doi:10.1186/s12958-024-00945-2.)

For this couple, the discovery was life-changing. Instead of cycling blindly, they could now make informed decisions: focusing on IVF with genetic screening rather than wasting time and emotional energy on medicated IUIs or natural attempts that carried a higher risk of miscarriage.

Karyotype Test vs. Other Genetic Tests

Patients often confuse karyotype testing with other forms of genetic testing, so here’s how they differ:

Test	Who It’s Done On	What it Detects	Purpose
Karyotype Test	Intended parents (blood test)	Chromosomal number and structure (e.g., translocations)	Diagnoses inherited structural abnormalities
Carrier Screening	Intended parents	Recessive genetic disorders (e.g., cystic fibrosis)	Identifies carrier status for disease genes
PGT-A / PGT-SR	Embryos	Chromosomal abnormalities or rearrangements	Screens embryos before IVF transfer

A karyotype test helps identify why embryos may not be viable in the first place. It’s not about finding someone to blame: it’s about finding answers.

Empowerment Through Information

The most heartbreaking part of this story isn’t the diagnosis: it’s how long it took to get there.

No couple should have to endure years of failed cycles and emotional devastation before someone asks a simple question. I’m not here to cast other clinics or physicians in a negative light, we are all human and falliable by nature. Even the best clinics and the most experienced doctors can miss something that is staring them right in the face. That’s why it’s so important that YOU become your strongest advocate for managing your care. It’s not about being suspicious or mistrustful, it’s about being informed. Knowing when to ask for a karyotype test could save you years of uncertainty.

Because sometimes, the key to unlocking years of unexplained infertility really does lie in one simple test.

In my upcoming book, The Lucky Egg, I dive deeper into the role of diagnostic tools like karyotype testing, HSG, and genetic carrier screening: not just as medical tests, but as powerful sources of clarity and empowerment. My hope is that readers walk away better equipped to ask questions, advocate for themselves, and understand the “why” behind their fertility journey.

If you’d like to stay up to date with my latest posts on fertility and reproductive health, I encourage you to follow me on Instagram and subscribe to my monthly fertility newsletter, The Lucky Egg Drop. If you are located in the NYC area and would like to see me in my office for a fertility consult, you can request an appointment here.