Genetics and fertility are more intimately connected than most couples undergoing fertility treatment are aware. Chromosomal abnormalities in embryos are the most common cause of both implantation failure and first-trimester miscarriage. Structural chromosomal rearrangements in one or both parents can produce aneuploid embryos at a high rate, causing recurrent pregnancy loss. Single gene disorders — inherited conditions caused by mutations in a single gene — can be transmitted to offspring in ways that affect their health and wellbeing profoundly.
And yet genetics is frequently the last dimension of fertility to be investigated — addressed, if at all, only after multiple failed cycles have raised enough clinical concern to prompt a karyotype test or a discussion of preimplantation genetic testing.
This article provides the complete picture of genetic causes of infertility and the clinical role of PGT — preimplantation genetic testing — in managing them. It explains the different genetic mechanisms that affect fertility, the specific clinical presentations that should prompt genetic investigation, the different types of PGT available and what each does, and the honest clinical evidence for when PGT produces meaningful clinical benefit and when its benefits are more limited.
Genetic Mechanisms That Affect Fertility
The genetic landscape of fertility involves three distinct levels of genetic organization, each with its own mechanisms and clinical implications.
Chromosomal Aneuploidy — the Most Common Genetic Cause
Aneuploidy — an incorrect number of chromosomes in a cell — is the most common genetic abnormality affecting human embryos and the most common cause of both implantation failure and first-trimester miscarriage.
Normal human cells contain 46 chromosomes — 23 pairs. An aneuploid cell has more or fewer than this number, typically because of errors in the separation of chromosome pairs during the formation of eggs or sperm. The most common mechanism is meiotic non-disjunction — the failure of a chromosome pair to separate correctly during egg formation, producing an egg with 22 or 24 chromosomes rather than the normal 23. When such an egg is fertilized by a normal sperm, the resulting embryo has 45 or 47 chromosomes — a monosomy or trisomy — rather than the normal 46.
The vast majority of aneuploid embryos either fail to implant or miscarry in the first trimester, because chromosomal imbalance of this degree is incompatible with normal development. A small number of trisomies are compatible with survival — most famously trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome) — but even these are associated with significant developmental challenges.
The rate of aneuploidy in eggs — and therefore in embryos — increases dramatically with maternal age. In women under 35, approximately 25 to 35 percent of eggs are aneuploid. By age 38 to 40, this proportion rises to approximately 50 to 60 percent. By age 42 to 44, it may approach 80 to 90 percent. This age-related increase in egg aneuploidy is the primary biological explanation for the well-documented decline in natural fertility and IVF success rates with advancing maternal age, and for the increasing miscarriage rates seen in older women.
Structural Chromosomal Rearrangements — Parental Carriers
Structural chromosomal rearrangements — in which segments of chromosomes are broken off and reattached in abnormal configurations — are present in approximately 1 to 2 percent of infertile couples and in approximately 3 to 5 percent of couples with recurrent pregnancy loss.
The most common types are balanced translocations — in which a segment from one chromosome has exchanged position with a segment from another chromosome. In a balanced translocation, the total amount of genetic material is correct — just rearranged. The carrier of a balanced translocation is typically completely healthy, because all of the genetic information is present. But when their gametes form, the rearranged chromosomes may be distributed unequally between eggs or sperm — producing gametes that, when fertilized, result in embryos with unbalanced chromosome complements. These unbalanced embryos typically fail to implant or miscarry.
For couples where one partner carries a balanced translocation, the proportion of embryos that are genetically unbalanced — and therefore non-viable — can be very high. Depending on the specific translocation, 50 to 75 percent of embryos produced may be unbalanced. This explains the pattern seen in translocation carrier couples — repeated IVF cycles producing multiple embryos but consistently poor implantation, or recurrent miscarriage after natural or assisted conception.
Single Gene Disorders — Monogenic Conditions
Single gene disorders — conditions caused by mutations in a single gene that are transmitted according to Mendelian inheritance patterns — represent a distinct category of genetic fertility concern. These are not conditions that typically cause infertility directly in the parent carriers. Rather, they are conditions that can be transmitted to offspring — with varying probability depending on the inheritance pattern — causing significant disease in affected children.
Autosomal recessive conditions — such as spinal muscular atrophy (SMA), cystic fibrosis, beta-thalassaemia, and sickle cell disease — are caused by mutations in both copies of a specific gene. Carriers of a single mutation are typically healthy. But when two carriers have children together, each pregnancy has a one in four chance of receiving the mutation from both parents and being affected by the condition.
Autosomal dominant conditions — in which a single mutation in one copy of the gene is sufficient to cause disease — include conditions such as Huntington's disease, myotonic dystrophy, and BRCA1/2-associated hereditary breast and ovarian cancer syndrome. An affected parent has a 50 percent probability of transmitting the condition to each child.
X-linked conditions — caused by mutations on the X chromosome — include conditions such as Duchenne muscular dystrophy, haemophilia, and Fragile X syndrome. Female carriers of X-linked recessive conditions typically do not manifest the condition themselves but have a 50 percent probability of transmitting the mutation to each son, who would be affected.
Types of PGT — What Each Does
Preimplantation genetic testing — performed on cells biopsied from embryos in an IVF cycle before transfer — encompasses several distinct tests, each targeting a different category of genetic abnormality.
PGT-A — Preimplantation Genetic Testing for Aneuploidies
PGT-A screens all 24 chromosome types in an embryo for numerical abnormalities — identifying embryos with the correct number of chromosomes (euploid) and those with too many or too few (aneuploid). Euploid embryos are selected for transfer; aneuploid embryos are not used.
The testing platform used in modern PGT-A is typically next-generation sequencing (NGS) or array comparative genomic hybridization (aCGH) — high-resolution techniques that can detect the gain or loss of chromosome segments across all chromosomes from the small number of cells biopsied from the embryo's trophectoderm.
PGT-A provides the most direct available approach to the problem of embryonic aneuploidy — identifying chromosomally normal embryos before transfer, rather than waiting for aneuploidy to manifest as failed implantation or miscarriage.
PGT-SR — Preimplantation Genetic Testing for Structural Rearrangements
PGT-SR is the specific testing approach used for couples in whom one or both partners carry a structural chromosomal rearrangement — balanced translocation, inversion, or other structural variant. PGT-SR tests embryos for the specific unbalanced chromosome complement that the parental rearrangement could produce, identifying embryos that have either a balanced or normal chromosome complement and are therefore appropriate for transfer.
For translocation carrier couples, PGT-SR dramatically improves the efficiency of IVF — by identifying the specific unbalanced embryos that would otherwise result in failed implantation or miscarriage, and selecting only the normal or balanced embryos for transfer.
PGT-M — Preimplantation Genetic Testing for Monogenic Conditions
PGT-M tests embryos for a specific single gene mutation known to be present in one or both parents. It requires prior work-up — genetic testing of both parents and, in most cases, reference samples from affected or unaffected family members — to design the specific molecular test for the family's specific mutation. Once the test is designed and validated, embryos in an IVF cycle are biopsied and tested, and only those without the relevant mutation are selected for transfer.
PGT-M allows couples at risk of transmitting serious single-gene conditions to have children who are not affected by the condition — without the need for prenatal diagnosis and the difficult decisions that a positive prenatal result creates.
When PGT Testing Is Recommended
The clinical recommendation for PGT is based on the specific clinical presentation — the category of genetic concern, the patient's age, and the clinical history.
PGT-A — Indications
Advanced maternal age (over 37 to 38 years): The rising aneuploidy rate in older women makes PGT-A particularly valuable in this group — by identifying the proportion of embryos that are euploid and therefore most likely to implant and sustain a pregnancy, PGT-A improves the efficiency of embryo selection and reduces the miscarriage rate per transfer. The clinical benefit of PGT-A in older women is well documented in multiple randomised trials and is most pronounced in women over 38 where the aneuploidy rate is high enough that a significant proportion of embryos in any given cohort will be aneuploid.
Recurrent implantation failure: When multiple embryo transfers of morphologically good embryos have failed without a specific explanation, undetected aneuploidy in the transferred embryos is a common contributing cause. PGT-A in subsequent cycles identifies euploid embryos and often produces implantation when morphological selection alone has repeatedly failed.
Recurrent pregnancy loss: When recurrent miscarriage has occurred and chromosomal analysis of miscarriage tissue has confirmed aneuploid losses — or where the clinical picture (older maternal age, multiple morphologically normal embryos failing) strongly suggests embryonic aneuploidy as the primary mechanism — PGT-A in an IVF cycle directly addresses the cause.
Previous aneuploid pregnancy: Couples who have had a previous pregnancy with a chromosomal abnormality — Down syndrome, Edwards syndrome, or any other trisomy — have an elevated risk of recurrence, and PGT-A in a subsequent IVF cycle can identify chromosomally normal embryos for transfer.
Severe male factor infertility: Men with severe oligospermia or non-obstructive azoospermia — particularly those with genetic causes including Klinefelter syndrome or Y chromosome microdeletions — produce sperm with higher rates of chromosomal abnormalities. Embryos produced from these sperm may have elevated aneuploidy rates, and PGT-A in these cases identifies the euploid embryos from what may be a small cohort.
Important Caveats About PGT-A
The clinical benefits of PGT-A are not universal — and honest communication about its limitations is as important as presenting its benefits.
For younger women with good prognosis: PGT-A in young women with good ovarian reserve, multiple good-quality blastocysts, and no history of recurrent loss or implantation failure produces a marginal benefit at best — because the baseline aneuploidy rate in young women is low, and the probability of selecting a euploid embryo by morphological assessment alone is already high. For these women, the cost of PGT-A — financial and the small biopsy risk — may not be justified by the incremental benefit.
PGT-A does not improve the cumulative live birth rate in all populations: Multiple large randomised trials have shown that PGT-A improves the live birth rate per transfer — by reducing the proportion of aneuploid embryos transferred — but does not consistently improve the cumulative live birth rate per stimulation cycle across all age groups. This is because PGT-A removes aneuploid embryos from the transfer pool — which would have failed anyway — but does not create new euploid embryos. In young women where most embryos are euploid, removing a small proportion of aneuploid ones has limited impact on the cumulative outcome.
Mosaic embryos require careful counseling: A proportion of biopsied embryos are reported as mosaic — containing a mixture of normal and abnormal cells. The clinical management of mosaic embryos is not fully resolved — some mosaics are capable of developing normally, and transferring selected mosaic embryos may produce healthy pregnancies. The decision about whether and when to transfer a mosaic embryo requires specific counseling and should be made at a center with experience in managing mosaic PGT-A results.
PGT-SR — Indications
PGT-SR is recommended for couples in whom parental karyotyping has identified a balanced translocation or other structural chromosomal rearrangement in either partner. The indication is specific and clear — the parental chromosomal rearrangement produces a high proportion of unbalanced embryos in natural or IVF conception, and PGT-SR identifies the unaffected embryos, dramatically improving the probability of a successful pregnancy per transfer and virtually eliminating the risk of transmitting the unbalanced rearrangement.
PGT-M — Indications
PGT-M is recommended for couples where both partners are confirmed carriers of the same autosomal recessive condition, where one partner has or carries an autosomal dominant condition with significant health impact, or where the female partner is a carrier of an X-linked condition. The specific conditions most commonly tested in the Indian context include beta-thalassaemia (for which India has extremely high carrier rates in specific communities), sickle cell disease, spinal muscular atrophy, cystic fibrosis, Duchenne muscular dystrophy, and hereditary cancer syndromes including BRCA1/2.
The prerequisite for PGT-M is genetic counseling — both to confirm the indication and to ensure the couple fully understands the implications of the testing, the probability of finding affected embryos, and the management of the various possible results.
The Role of Genetic Counseling
Genetic testing in the context of fertility — whether karyotyping, preimplantation genetic testing, or carrier screening — generates information that extends beyond the immediate fertility treatment decision. It affects the couple's understanding of their own health, the health implications for their future children, the relevance for other family members who may carry the same genetic variants, and — in some cases — decisions about whether to pursue treatment at all.
Genetic counseling — provided by a trained genetic counselor or by a clinician with specific expertise in reproductive genetics — is an essential component of the care provided to couples for whom genetic testing is relevant. At Metro IVF, genetic counseling is integrated into the clinical care of every couple for whom genetic investigation or preimplantation genetic testing is being considered.
The counseling discusses the specific genetic finding, its inheritance and implications, the PGT options available, the probability of finding affected versus unaffected embryos, and the decisions the couple faces based on the results. It is provided before testing begins — as informed consent — and after results are available, as clinical guidance.
What Couples With Genetic Concerns Should Know
The message this article is written to deliver to couples who have a known or suspected genetic contribution to their infertility is this: genetic causes are identifiable, their contribution to fertility outcomes is quantifiable, and in most cases the clinical approach that follows from genetic investigation — whether PGT-SR for translocation carriers, PGT-A for age-related aneuploidy, or PGT-M for monogenic conditions — meaningfully improves the probability of a successful pregnancy.
Genetic investigation is not a reason to give up. It is a reason to treat the specific cause with the specific tool that the cause requires.
And at Metro IVF in Ambikapur, that investigation — complete, honest, and followed by the treatment it indicates — is available.
Your Next Step
If you have a family history of genetic conditions, have been told you carry a chromosomal abnormality, have experienced recurrent miscarriage, or are over 37 and considering IVF — a consultation with Dr. Ashish Soni at Metro IVF in Ambikapur provides the most complete genetic assessment and PGT guidance available in the region.
The genetic dimension of your fertility is worth understanding. And understanding it — specifically, with the right clinical guidance — changes what is possible.
Metro IVF Test Tube Baby Center Ambikapur, Chhattisgarh metrofertility.in Led by Dr. Ashish Soni — North India's First Fertility Super Specialist
Genetic causes of infertility have specific solutions. Book your consultation with Dr. Ashish Soni at Metro IVF today — and find out what yours are.