During this event, Yulian Melnyk, Senior Embryologist at LLC Medicover Ukraine, explained egg development and the stages where problems can occur.
In his presentation, Yulian Melnyk approached one of the most frustrating and emotionally difficult questions in fertility treatment: why eggs sometimes fail to mature, fertilise, or develop into viable embryos, even when stimulation appears to be successful.
From an embryologist’s perspective, he explained that eggs are often discussed as numbers, such as follicle count or oocyte yield, but “oocytes are not just numbers.” Each egg carries a complex biological history that begins long before birth, and understanding this background is essential for interpreting IVF outcomes.
Many treatment disappointments, he noted, cannot be explained by stimulation protocols alone. Instead, they are rooted in fundamental biological processes that influence egg competence at a cellular and molecular level.
Yulian explained that the story of an egg starts during fetal life. Primordial germ cells develop into oogonia, which then become primary oocytes before birth. These oocytes enter meiosis and remain arrested in a specific phase, prophase I, for many years.
This prolonged arrest is unique and significant. “Meiosis in oocytes may take years,” he explained, unlike mitosis, which is rapid and occurs in most tissues. Only after a luteinising hormone (LH) surge shortly before ovulation does meiosis resume, allowing the egg to complete its final maturation steps and prepare for fertilisation.
This long arrest period makes oocytes particularly vulnerable to errors, especially as maternal age increases.
To understand where development can go wrong, Yulian reviewed the hormonal regulation of the menstrual cycle. Follicle-stimulating hormone (FSH) and luteinising hormone (LH) stimulate the growth of multiple follicles, but typically only one becomes dominant, while the others undergo atresia.
As follicles grow, estradiol levels rise, preparing the endometrium, cervix, and fallopian tubes for fertilisation. When estradiol reaches a peak, an LH surge triggers ovulation approximately 24 hours later. After ovulation, granulosa cells transform into the corpus luteum and begin producing progesterone.
Any disruption in this finely regulated process, whether hormonal, cellular, or genetic, can affect egg maturation and quality.
From an embryologist’s point of view, Yulian classified the causes of impaired egg development into three broad categories:
genetic disorders
cytoplasmic and mitochondrial disorders
exogenous and environmental factors
Each category can independently or collectively compromise egg competence and embryo development.
Genetic abnormalities are a major cause of failed egg development. During meiosis, chromosomes must separate correctly. Errors in this process lead to aneuploidy, where eggs contain too many or too few chromosomes.
Yulian explained that human oocytes are particularly prone to chromosome segregation errors, especially during the first and second meiotic divisions. Autosomal aneuploidy is usually lethal, leading to failed implantation or early pregnancy loss, while sex chromosome abnormalities may result in developmental anomalies.
He emphasised that:
Aneuploidy is the leading cause of reproductive failure and birth defects in humans.
The strong association between maternal age and aneuploidy, combined with the trend toward later parenthood, means this issue is becoming increasingly common.
A rare but significant genetic issue discussed was oocyte maturation arrest. In these cases, IVF cycles may yield immature or degenerated oocytes rather than the expected mature eggs.
Yulian described three main presentations:
complete arrest of oocyte maturation
empty follicle syndrome
ovarian resistance to stimulation
Research suggests that these conditions are often linked to genetic factors affecting oocyte maturation pathways. Importantly, he stressed that this is not the patient’s fault. “It is a biological trait,” he explained, and one that currently requires further scientific research.
Beyond genetics, the internal structure of the oocyte cytoplasm plays a crucial role in fertilisation and early embryo development.
Yulian described several cytoplasmic abnormalities, including refractile bodies, central cytoplasmic granulation, smooth endoplasmic reticulum (SER) clusters, and vacuoles. Some of these abnormalities are not visible during routine screening but become apparent once embryologists examine the oocytes in the laboratory.
SER clusters, in particular, are associated with genetic abnormalities in embryos. Vacuoles may indicate metabolic disturbances or degeneration and are often seen in oocytes from hyperstimulated ovaries or suboptimal stimulation protocols. He noted that with an adjusted stimulation strategy, vacuoles may be absent in subsequent cycles.
Cytoplasmic integrity also includes proper centrosome function. The centrosome organises microtubules and is essential for the fusion of male and female genetic material.
During fertilisation, the sperm provides the centriole, while the oocyte supplies the proteins needed to form the sperm aster, a structure essential for successful fertilisation and early embryo development.
Centrosome dysfunction, Yulian explained, is an often hidden but significant cause of male infertility. It is associated with conditions such as globozoospermia, fibrous dysplasia, and abnormal sperm aster formation. These defects may be genetic or acquired through toxins or epigenetic influences.
Mitochondrial disorders were described as Yulian’s “favourite topic” because of their profound impact on egg competence.
Mitochondria provide the energy required for chromosome segregation, fertilisation, and embryo development. With age, mitochondria undergo swelling, vacuolisation, and structural disruption, reducing energy production and membrane potential.
Although embryologists cannot see mitochondrial damage directly, its effects are evident in poor embryo development, reduced implantation rates, and chromosomal instability.
Studies have shown reduced expression of mitochondrial regulatory genes in cumulus granulosa cells from women with diminished ovarian reserve, along with lower mitochondrial DNA content. This negatively affects oocyte quality and developmental competence.
Yulian also discussed mitochondrial aggregation within the egg. When mitochondria cluster centrally, they can physically displace the nucleus toward the cell periphery, disrupting normal cell division, symmetry, and nuclear integrity.
This imbalance leads to reduced DNA replication, increased damage, and altered transcription, all of which compromise embryo viability. Maintaining a dispersed mitochondrial distribution is therefore critical for healthy embryo development and may explain why some IVF cycles fail despite apparently normal parameters.
The final category discussed was exogenous and environmental factors. Oocytes are highly sensitive to external influences, including toxins, medications, and lifestyle choices.
Endocrine disruptors such as bisphenol A, phthalates, and pesticides can interfere with hormonal signalling and follicle development. Medications, including ovulation induction drugs and contraceptives, may affect oocyte maturation depending on dosage and stimulation strategy.
Radiation and chemotherapy can damage DNA and ovarian reserve, often leading to premature ovarian failure. Lifestyle factors such as smoking, alcohol consumption, and poor nutrition negatively affect cytoplasmic integrity and oocyte morphology.
Understanding these influences allows clinicians and embryologists to adapt treatment strategies and reduce avoidable risks.
Yulian concluded with practical advice designed to empower patients:
seek medical advice early, especially after 12 months of trying or 6 months if over 35
remember that infertility affects both partners
complete a full fertility workup, including hormonal testing and semen analysis
adopt a healthy lifestyle, including balanced nutrition and avoidance of toxins
understand personal and environmental risk factors
While some causes of poor egg development cannot be changed, early intervention, informed decision-making, and personalised care can make a meaningful difference.
From an embryologist’s perspective, egg development is influenced by a complex interplay of genetics, cellular structure, energy metabolism, and environment. Many failures occur silently, long before fertilisation or embryo transfer.
As Yulian Melnyk emphasised throughout his presentation, understanding these hidden mechanisms helps explain why IVF outcomes vary and why patience, realistic expectations, and individualised treatment are essential parts of the fertility journey.
Age strongly correlates with genetic disruptions during oocyte maturation, as I showed in the presentation. Morphologically good embryos do not necessarily mean they are genetically normal. This is the main issue.
Regarding egg quality, a healthy lifestyle is a key factor and something that can still be addressed now. However, some genetic disorders cannot be corrected by lifestyle alone. Together with the embryologist and reproductive specialist, an individual approach is needed, as the problem may not be limited to egg quality alone.
This is usually related to stimulation, but genetic testing may also be considered to understand whether there is a deeper underlying cause.
This depends on the individual and the specific deficiencies. The best approach is to consult a fertility specialist, perform blood tests first, identify any deficiencies, and then supplement accordingly. This should always be individualised.
Yes, it can be different, although not always. The first stimulation cycle is often informative and helps us understand how the ovaries respond. Based on that, stimulation can be adjusted in subsequent cycles.
This does not mean that a healthy pregnancy cannot result from the first cycle. Fertility is multifactorial, and sometimes repeated attempts are necessary.
In such cases, I would first review all embryological parameters to ensure they were within normal ranges. I would also compare outcomes in patients of similar age using the same incubator to exclude laboratory factors.
The cause may be genetic or related to fertilisation. Fragmentation can also represent the embryo removing cellular waste, and embryos may have some capacity for self-repair.
I would review the sperm analysis, including DNA fragmentation testing, and reassess the stimulation protocol. When we consistently retrieve fewer mature oocytes than expected, stimulation needs to be reviewed. This requires a step-by-step approach.
We are currently conducting trials. This technology is controversial and not yet sufficiently supported by evidence. Before recommending it clinically, we must be sure it is not being used prematurely. These trials are not open to patients.
Yes, because fertilisation involves exchanges between sperm and oocytes, and meiosis is prone to errors, especially with advanced maternal age. The chances of a healthy pregnancy are lower, but not zero, and they decline gradually with age.
Inappropriate stimulation can affect egg quality. However, high doses alone do not necessarily mean the stimulation was incorrect. Clinicians adapt dosage based on duration, BMI, and previous cycles.
In our laboratory, we usually transfer blastocysts on day 5 or 6, which we consider optimal. Some clinics achieve comparable results with day 3 transfers. Advances in culture systems now make day 5 transfer the most common approach.
Age significantly affects fertility chances, but outcomes vary. Even younger women can experience fertility issues. It is advisable to undergo a full fertility evaluation. Lifestyle improvements may help, but they cannot guarantee success.
PGT-A is generally recommended for women over 35, those with previous miscarriages, unsuccessful cycles, or known genetic conditions. This decision must always be individualised.
Yes, but testing must begin with general genetic screening and then proceed to targeted testing based on findings. This is individualised for each patient.
Yes. I am not against blastocysts with lower trophectoderm grading, provided there is a visible inner cell mass. There are no “bad” blastocysts, only those with higher or lower priority.
PICSI was developed for cases where morphologically normal sperm cannot be reliably selected. These techniques have limits, and additional tests such as HBA (Hyaluronan Binding Assay) or DNA fragmentation testing may guide selection.
Poor nutrition affects general health and oocyte quality, but BMI alone is not sufficient to assess this. Egg donors are thoroughly screened, including fertility history, age, and ovarian reserve.
DNA fragmentation can vary between donations. In donor programmes, sperm quality is assessed based on age, health, and proven fertility.
If sperm factors have been excluded, the issue may lie with the oocytes. However, I always recommend seeking a second opinion to properly assess chances before making a final decision.
Fresh eggs generally have slightly higher efficiency because vitrification and warming add extra manipulation. However, success rates are now very similar, and both options have advantages depending on the clinical situation.
