A perfectly graded, “high-quality” embryo doesn’t always lead to pregnancy, and that fact can be one of the harshest truths to accept in IVF.
Success depends on more than the appearance and grade of embryos, because IVF is a complex process. This article presents the 10 common reasons IVF may fail despite good embryos and what you can do to improve your chances of a successful cycle.
What causes IVF to fail?
Beyond embryo quality, IVF success depends on numerous biological, medical, and environmental factors. Sometimes, positive outcomes come down to chance, as an embryo may not implant even under ideal conditions.
Below are some of the common reasons why IVF fails, followed by a closer look at the potential reasons:
Genetic factors
Subtle sperm defects
Hormonal imbalance
Immune system response
Underlying medical conditions
Uterine health issues
Lifestyle factors and stress
Subpar lab conditions and transfer technique
1. Genetic factors
Once embryos have been created in the lab, embryologists carefully monitor their development, paying attention to their cell number, symmetry, fragmentation, and pace of expansion. Based on these factors, they determine the embryo's quality and grade it.
However, standard embryo grading is based on appearance under the microscope. An embryo may look perfect and be given a high grade, but grading can’t reveal whether it has chromosomal abnormalities that prevent implantation and cause miscarriage.
Maternal age plays a big role here because as women age, eggs are more likely to carry genetic errors, and those errors can be passed on to the embryo, even if it looks high quality. That’s why IVF success rates per cycle decline steadily with age:
Age group | IVF success rates (live births) |
|---|---|
<35 | 54% |
35–37 | 40.5% |
38–40 | 26% |
41–42 | 13.3% |
>42 | 4% |
Data source: Society for Assisted Reproductive Technology
The good embryo that was transferred may not have been genetically viable, which is why preimplantation genetic testing (PGT) is necessary to identify embryos with the highest chance of success.
For example, when a parent carries a chromosomal rearrangement, such as a balanced translocation, it doesn't usually cause symptoms in the carrier. Still, it can result in embryos with missing or extra genetic material and lower the chances of success.
Beyond chromosomal issues, inherited genetic conditions can impact both embryo viability and health. For instance, if both parents carry a mutation of the same gene, the embryo that carries the two copies may stop developing or fail to implant. In rare cases where the pregnancy is successful, the child may face serious health challenges after birth.
💡Bonus info!
To see beyond what the microscope shows, most fertility clinics have introduced PGT as a part of the treatment. The main types of embryo genetic screening include:
PGT option | What it detects |
|---|---|
Screens for extra or missing chromosomes that cause failed implantation or miscarriage | |
Tests for specific inherited single-gene disorders, such as:
| |
Detects structural rearrangements, such as:
| |
Polygenic embryo screening that provides insights into long-term risk for chronic, late-onset conditions, such as:
|
Source: Tima Miroshnichenko
2. Subtle sperm defects
Even when an embryo appears morphologically strong, sperm quality still matters. The conventional semen analysis only gives a partial view (count, motility, and shape). Below the surface, sperm DNA damage or fragmentation can undermine embryo viability, implantation, or early pregnancy maintenance. This may not always be obvious from embryo grading alone.
In a study of more than 6,300 IVF and ICSI cycles, researchers examined sperm DNA fragmentation and found that couples with higher fragmentation had similar fertilization and pregnancy rates to those with low fragmentation. However, their risk of miscarriage was significantly higher.
Even when a good embryo implants, hidden sperm DNA damage can cause the pregnancy to fail.
It’s important to note that up to 15% of men with a normal semen analysis may still have faulty sperm DNA. That’s why the sperm DNA fragmentation test is recommended, especially when unexplained implantation failure or miscarriage occurs.
3. Hormonal imbalance
Hormones are essential to every stage of IVF, from egg maturation and ovulation to endometrial receptivity and early embryo development. Even slight hormone level imbalances can interfere with the implantation process and increase the risk of miscarriage.
Common hormonal issues that may affect IVF success include:
Estrogen and progesterone imbalance: Disrupts the ability of the uterine lining to receive and support the embryo
Thyroid disorders (hypothyroidism and hyperthyroidism): Can impair ovulation, implantation, and early pregnancy maintenance
Many hormonal imbalances can be detected and corrected with medication, including hormone supplementation and lifestyle adjustments.
4. Immune system response
In a typical pregnancy, the immune system adjusts to tolerate the embryo, which contains genetic material from both parents. But sometimes, especially in people with pre-existing immunological conditions, the body may mistakenly treat the embryo as a threat and attack it.
If you’ve experienced two or more failed IVF cycles, discuss immune system testing with your fertility specialist.
Source: RDNE stock project
5. Underlying medical conditions
IVF failure can be linked to undiagnosed or poorly managed medical conditions, which may interfere with hormone regulation and overall reproductive health.
Here’s an overview of the most common conditions that can impact IVF outcomes:
Polycystic ovary syndrome (PCOS) | Hormonal imbalance, inflammation, and reduced endometrial receptivity in PCOS can lower implantation chances. Women with PCOS also have a higher risk of miscarriage, gestational diabetes, and preeclampsia. |
|---|---|
Endometriosis | The condition causes tissue similar to the uterine lining to grow outside the uterus. This can lead to inflammation, scarring, and changes in the pelvic environment. |
Autoimmune disorders | Conditions like lupus or autoimmune thyroiditis can cause the immune system to attack the body’s own tissue, including reproductive organs and embryos. |
Diabetes | Poorly controlled blood sugar levels can disrupt hormone balance and disrupt endometrial receptivity, increasing miscarriage risk and making implantation and healthy development harder. |
Insulin resistance | Often seen in PCOS, insulin resistance may interfere with endometrial receptivity. |
Pro tip 💗
Millions of people carry DNA variants linked to serious diseases, but over 90% don’t know it. Some health risks that affect fertility aren’t visible with standard tests and are only discovered after multiple failed IVF attempts.
Nucleus Family offers a clinical-grade, at-home DNA test that helps you uncover genetic risks for over 2,000 conditions, from hormonal and metabolic issues to immune system health. It’s also a carrier screening test, helping you identify whether you or your partner carry genetic variants that could be passed on to a child. You’ll also get access to genetic counselors who can help you with the next steps in health management.
6. Uterine health issues
Even with a high-quality embryo, implantation won’t succeed unless the uterus is ready to receive it. Structural issues in the uterus can prevent the embryo from implanting and developing, or increase the risk of miscarriage later.
Uterine conditions that can affect IVF include:
Fibroids: Noncancerous growths that distort the shape of the uterus
Polyps: Small growths in the uterine lining
Adhesions and scar tissue: Often caused by previous surgery or infections
Thin or overly thick endometrium: Impaired uterine lining may not support implantation
Congenital uterine abnormalities: Septate uterus or other structural issues present from birth
7. Lifestyle factors and stress
Although IVF is a medical procedure, your everyday habits and general well-being can influence its outcomes. High stress, poor nutrition, smoking, alcohol, and other habits may affect your body’s response to the embryo.
Even small changes can make a difference, so here’s what to focus on:
Quit smoking at least three months before IVF
Limit or avoid alcohol
Focus on balanced meals with whole foods and adequate protein amounts
Maintain a healthy weight as both being underweight and overweight can interfere with implantation and pregnancy
Manage stress through moderate exercise, mindfulness, or therapy
Avoid products with toxic chemicals
Source: Alex Green
8. Subpar lab conditions and transfer technique
The environment where embryos are created and handled is delicate, and even small deviations can have a significant impact. While in the lab, embryos are highly sensitive to fluctuations in:
Temperature and pH
Oxygen and carbon dioxide levels
Humidity
Light exposure
Culture media composition
The embryo transfer technique can also influence implantation success. Even minor trauma or incorrect placement can lower the chances of success. Variables such as the catheter used and the depth and angle of insertion also matter.
To boost success rates, many clinics perform mock transfers before the actual procedure. Consider asking fertility teams about this while you’re exploring clinics.
Source: RDNE stock project
If IVF failed, what can you do next?
A failed IVF cycle can feel devastating, so allow yourself time to heal, rest, and process everything. Once you’re ready, meet with your fertility team to understand why the cycle may have failed and what your next steps should be.
Your doctors can observe and make adjustments to fine-tune your treatment or suggest alternatives, including:
Adjusting ovarian stimulation or transfer protocol
Adding tests or procedures to improve uterine receptivity
Considering donor eggs and/or sperm
Exploring gestational surrogacy if implantation is the issue
Before starting again, you may also want to look deeper into embryo selection, especially if your previous IVF failed with good embryos. Proper testing can reveal issues that standard grading may miss.
Nucleus IVF+ can be your support system during various demanding IVF stages. We offer integrated solutions and tools that guide you through every step, before, during, and after IVF. Nucleus gives you access to:
24/7 support from genetic counselors
An exclusive network of clinics, physicians, and testing options
Genetic optimization tool (before embryo selection)
Egg and sperm donors
Screening for 2,000+ genetic conditions — and more!
Make your IVF journey easier with Nucleus IVF+
Nucleus offers a wide selection of services to make your IVF journey less stressful. From testing parental DNA to preconception screening and embryo selection, Nucleus helps you with personalized guidance as you plan your next IVF cycle.
The platform offers unique products and solutions for different decision-making points, including:
Nucleus Family: Comprehensive DNA screening for hundreds of conditions you could unknowingly pass on to your kids. Understand how your genes may affect fertility, miscarriage risk, egg/sperm quality, or potential conditions that could impact your pregnancy or long-term health.
Nucleus Embryo: The first genetic optimization platform of its kind that helps you compare embryos for transfer. Nucleus uses the genetic testing data of embryos to help you evaluate them side by side in an interactive dashboard. You can sort them based on 2,000+ factors, including:
Health: For conditions like diabetes, heart disease, certain cancers, and rare inherited disorders like cystic fibrosis, muscular dystrophy, and hemophilia
Traits: Height, BMI, hair and eye color, hair texture, muscle strength, and more
Well-being: Markers linked to mental health, cognitive abilities, sleep patterns, and more
Depending on the stage of your fertility journey, you can explore the Nucleus IVF+ solution that comes with all-inclusive IVF benefits, including concierge support, genetic screening for both parents, ICSI included with the cycle, PGT, unlimited genetic counseling, and more. You’ll also get end-to-end support when choosing clinics and donors, if necessary.
Featured image source: Engin Akyurt
