Introduction

Genetics plays a significant role in fertility treatments. Infertility affects approximately 10% of the reproductive-age population, with about 1 in 6 people worldwide experiencing infertility challenges. Understanding the genetic factors behind these issues is crucial for effective treatment.

Assisted reproductive technologies (ART), such as in vitro fertilization (IVF), are pivotal in addressing infertility. ART includes advanced procedures like Preimplantation Genetic Diagnosis (PGD), Preimplantation Genetic Screening (PGS), and Preimplantation Genetic Testing (PGT). These techniques enhance the chances of conception by selecting embryos with the best genetic health.

Key Takeaway: The integration of genetics in fertility treatments, through methods like PGD, PGS, and PGT, can significantly improve your chances of successful conception.

Understanding the Genetic Factors Behind Infertility

Genetic factors play a crucial role in infertility, often manifesting through specific genetic disorders or chromosome problems. These genetic abnormalities can interfere with reproductive processes, leading to challenges in conception.

The Importance of Understanding Inheritance Patterns in Fertility

Understanding inheritance patterns is vital for identifying potential genetic risks associated with infertility. These patterns can reveal whether certain conditions are likely to be passed down from one generation to the next.

• Autosomal Dominant Inheritance: A single copy of the mutated gene can cause the disorder.
• Autosomal Recessive Inheritance: Two copies of the mutated gene are required for the disorder to manifest.
• X-linked Inheritance: Disorders linked to genes on the X chromosome, affecting males more severely than females.

Recognizing these patterns helps tailor fertility treatments and provides valuable insights into potential outcomes for couples facing infertility challenges.

Genetic Testing Options for Couples Facing Infertility

Genetic testing methods are essential tools for couples dealing with infertility, providing crucial insights into underlying genetic issues. Various tests are available to identify potential genetic causes of infertility:

1. Karyotype Tests

These tests analyze the number and structure of chromosomes in a person’s cells. They help identify chromosomal abnormalities such as translocations, inversions, or aneuploidies that can lead to infertility or recurrent miscarriages. For instance, a balanced translocation in one of the partners might cause implantation failure or early pregnancy loss.

2. Expanded Carrier Screening

This method screens for a wide range of recessive genetic diseases that could affect offspring. By identifying carrier status for conditions like cystic fibrosis, spinal muscular atrophy, or fragile X syndrome, couples can make informed decisions about their reproductive options.

Both karyotype tests and expanded carrier screening play vital roles in diagnosing genetic factors contributing to infertility. By understanding these genetic elements, healthcare providers can better tailor fertility treatments to improve the chances of successful conception.

Preimplantation Genetic Testing (PGT): Optimizing Embryo Selection During IVF

Preimplantation genetic testing (PGT) is a crucial procedure in the realm of assisted reproductive technologies. It encompasses two primary types: preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS).

1. Preimplantation Genetic Diagnosis (PGD)

This process involves testing embryos for specific genetic disorders that one or both parents are known carriers of. PGD helps prevent the transmission of inherited conditions such as cystic fibrosis or sickle cell anemia.

2. Preimplantation Genetic Screening (PGS)

Unlike PGD, PGS examines embryos for chromosomal abnormalities that are not linked to a known parental condition. It identifies issues like aneuploidy, where embryos have missing or extra chromosomes, which can lead to failed implantation or miscarriage.

How PGT Enhances IVF Success Rates

By selecting genetically healthy embryos through PGT, the chances of a successful in vitro fertilization (IVF) cycle significantly improve. Healthy embryos are more likely to implant successfully and develop into viable pregnancies. This selection process:

• Reduces Miscarriage Rates: By ensuring embryos have the correct number of chromosomes, the risk of miscarriage due to chromosomal abnormalities decreases.
• Increases Live Birth Rates: Couples experience higher live birth rates as only the most viable embryos are chosen for transfer.

Including PGT in your fertility treatment plan at a reputable clinic like Genetics and Fertility, which offers advanced services such as IVF, IUI, ICSI, PGD, PGS and more, can enhance your chances of conception and lead to healthier pregnancy outcomes.

The Benefits and Considerations of PGT in Fertility Treatments

Reducing Miscarriage Risks

Preimplantation Genetic Testing (PGT) significantly reduces the risk of miscarriage. By selecting embryos with the correct chromosome count, PGT ensures that only genetically healthy embryos are implanted, thereby decreasing the chances of genetic abnormalities that often lead to miscarriage.

Identifying Suitable Candidates for PGT

PGT is particularly beneficial for specific groups:

• Women over 37 years old: Age-related chromosomal abnormalities increase with maternal age.
• Couples at risk for genetic diseases: Those with a history of inherited disorders.
• Individuals with recurrent miscarriages: Helps identify underlying genetic issues.

Using PGT not only improves IVF success rates but also provides peace of mind by minimizing the emotional and physical toll associated with repeated IVF failures.

Tailoring Fertility Treatments with Genetic Information at Fertility Center and Applied Genetics of Florida

Integrating genetic information into fertility treatments is transforming personalized medicine in the field. At the Fertility Center and Applied Genetics of Florida, genetic insights are used to create customized treatment plans that specifically address the unique genetic makeup of each couple or individual.

How Genetic Information Enhances Treatment Plans:

• Customized Medication Plans: Genetic screening helps identify how individuals metabolize various medications, allowing for precise dosage adjustments.
• Targeted Interventions: By understanding specific genetic mutations, doctors can recommend specific interventions that address underlying issues directly.
• Enhanced Embryo Selection: Utilizing preimplantation genetic testing (PGT), clinics can select the healthiest embryos, increasing the chances of a successful pregnancy.

Examples from Leading Clinics:

1. Precision Medicine Approach: Clinics use comprehensive genomic profiling to tailor treatments, optimizing hormone therapies based on genetic susceptibility.
2. Risk Management: Genetic data helps in assessing risks for conditions like PCOS or endometriosis, allowing for preemptive measures in treatment protocols.
3. Advanced Screening Methods: Implementing expanded carrier screenings ensures that couples are aware of potential hereditary conditions, enabling informed decisions about their reproductive journey.

At Fertility Center and Applied Genetics of Florida we consider both medical history and genetic predispositions. This approach not only enhances fertility treatment outcomes but also provides peace of mind for prospective parents by addressing potential challenges proactively. The positive feedback from patients further attests to the effectiveness of this approach, as seen in their reviews.

Conclusion: The Role of Genetics in Successful Fertility Treatments at Fertility Center and Applied Genetics of Florida

Using genetic information in fertility treatments can greatly increase the chances of getting pregnant. If you live in the Tampa Bay area, considering options like PGD, PGS, and PGT procedures is a proactive step toward making your dream of becoming a parent come true.

The Fertility Center and Applied Genetics of Florida specializes in using advanced genetic knowledge to improve fertility treatments. Contact us to find out how these innovative methods can assist you in your fertility journey, giving you more assurance and success.

The top image: Fertility © Poppypixstock

In the March issue of Obstetrics & Gynecology journal published by the American College of Obstetrics and Gynecology (ACOG) there are two committee opinions that recommend expanded carrier screening for recessive genetic disorders.

This is due to the lower costs of expanded testing in our current age of “Genomic Medicine.”  Pre-conception genetic screening gives future parents valuable information as there are currently commonly employed technologies that can prevent the birth of an affected child.  Couples have the very viable option of Pre-implantation Genetic Disease (PGD) screening of embryos through “in vitro” fertilization procedures.  The committee opinions are well written and I plan to use them as part of my informed consent process.

First, some basic notions:

” Carrier genetic screening is a term used to describe genetic testing that is performed on an individual who does not have any overt phenotype for a genetic disorder but may have one variant allele within a gene(s) associated with a diagnosis. Information about carrier screening should be provided to every pregnant woman. Carrier screening and counseling ideally should be performed before pregnancy because this enables couples to learn about their reproductive risk and consider the most complete range of reproductive options. A patient may decline any or all screening.”

Fair enough. It makes a lot of sense to be informed beforehand about any adversity you might encounter on your path.

” When an individual is found to be a carrier for a genetic condition, his or her relatives are at risk of carrying the same mutation. The patient should be encouraged to inform his or her relatives of the risk and the availability of carrier genetic screening. If an individual is found to be a carrier for a specific condition, the patient’s reproductive partner should be offered testing in order to receive informed genetic counseling about potential reproductive outcomes. If both partners are found to be carriers of a genetic condition, genetic counseling should be offered. “

Here is an excerpt from the committee’s recommendations:

• Ethnic-specific, pan-ethnic, and expanded carrier screening are acceptable strategies for prepregnancy and prenatal carrier screening. Each obstetrician–gynecologist or other health care provider or practice should establish a standard approach that is consistently offered to and discussed with each patient, ideally before pregnancy. After counseling, a patient may decline any or all carrier screening.
• If a patient requests a screening strategy other than the one used by the obstetrician–gynecologist or other health care provider, the requested test should be made available to her after counseling on its limitations, benefits, and alternatives.
• All patients who are considering pregnancy or are already pregnant, regardless of screening strategy and ethnicity, should be offered carrier screening for cystic fibrosis and spinal muscular atrophy, as well as a complete blood count and screening for thalassemias and hemoglobinopathies. Fragile X premutation carrier screening is recommended for women with a family history of fragile X-related disorders or intellectual disability suggestive of fragile X syndrome, or women with a personal history of ovarian insufficiency. Additional screening also may be indicated based on family history or specific ethnicity.

Essentially, their recommendations are all common sense: gather all information that’s possible at the moment, consult with a specialist, get clear understanding of the meaning of it, make your informed decision.

The committee opinions are clear and very well written. Our Clinic has been on the forefront of pre-implantation genetic testing (both, genetic screening and genetic  diagnosis) for our patients from the very beginning. And as I commented earlier, we plan to use the recommendations as part of our informed consent process.

You can read the ACOG Journal here.

Improving PGS Success with PGS Testing video in Spanish

Improving PGS Success with PGS Testing video in Portuguese

Improving PGS Success with PGS Testing video in Mandarin

Improving PGS Success with PGS Testing video in Japanese

Also:

Pre-Implantation Genetic Testing Services

Genetic disorders we screen for

Fertility Center & Applied Genetics of Florida partners with leading genetic testing laboratory CooperGenomics to bring you the most advanced Preimplantation Genetic Testing (PGD & PGS) available. CooperGenomics is a trusted leader in embryo testing and our partnership with them brings medicine from the lab bench to the bedside. Here are some of the benefits of partnering with the experts at CooperGenomics:

• CooperGenomics has over 20 years’ experience in preimplantation genetic testing;
• The expert scientists behind CooperGenomics performed the first ever PGS and PGD procedures and are truly pioneers in the field;
• CooperGenomics has an experienced team of board-certified genetic counselors who will work with your family and our team to review testing processes, discuss results, and answer questions, making sure you feel empowered and informed.
• CooperGenomics offers most robust and sophisticated PGS technology available. Compared to other lower resolution technologies, CooperGenomics’ high resolution PGS is performed on a Next Generation Sequencing (NGS) platform and is the only technology validated for the reliable detection of mosaicism. This gives our team the peace of mind we need to transfer the best possible embryo and give you the best chance at getting pregnant.

Preimpantation Genetic Screening PGS Whiteboard video

Preimpantation Genetic Diagnostics PGD Whiteboard video

A very nice patient who is also a nurse was seen in our Bonita Springs office today.  She is preparing for IVF in the coming weeks and was seen for her practice embryo transfer and other tests.  We were visiting and discussing the plans.  She indicated that she was interested in doing PGS “in order to increase her chance of pregnancy.”

PGS stands for pre-implantation genetic screening.  It is an added procedure during the IVF treatments.  Our clinic performs the embryo biopsies at the blastocyst stage in order to get more accurate results that when a day 3 biopsy is done.  The PGS gives the physician and the patient information about the genetic makeup of the embryo.  PGS results tell us if the embryo in question is expected to have 23 pairs of chromosomes or if it has an abnormal number of chromosomes like is seen in down’s syndrome where the embryo has an extra chromosome 21.

In the past and in most cases of IVF currently, the embryos are chosen based on their appearance.  Unfortunately, embryos can look completely normal and be genetically abnormal.  Abnormal embryos (with abnormal number of chromosomes) are the most common cause of implantation failure, IVF failure, and miscarriages.

In addressing this particular patient, I explained to her that “more technology is not always better.”  I explained that in her particular case the chance that the PGS information would increase her chance of pregnancy depended on the number of eggs and subsequent embryos that she made. If she were to respond conservatively to the ovarian stimulation and make few eggs, then the PGS would probably not increase her chance of pregnancy over the routine IVF where 2 or three embryos are selected based on their appearance.

If a patient makes fewer eggs, the PGS will just serve to give information and prevent the implantation or transfer of an abnormal embryo that would result in no pregnancy, a miscarriage, or even an abnormal fetus.  Fortunately, mother nature is quite good at preventing abnormal embryos from growing.  Please refer to the maternal age and reproduction web page at www.drpabon.com or www.geneticsandfertility.com

One other confounding issue is that I believe PGS can help in most cases because it can change clinical treatment and outcomes.  This is because when PGS is done at the blastocyst stage, the information is so good that we most often do a single embryo transfer.  This virtually eliminates the risk of twins and higher order pregnancies regardless of age.  So, the chance of pregnancy per transfer is higher, but some patients don’t have a transfer because all the embryos are abnormal by PGS or so abnormal they don’t develop to the biopsy stage.

This very nice patient should understand that it is ok to use technology when the use of the technology matches her goals and that sometimes the added cost of the additional technology may not increase her overall chance of pregnancy unless there is a good number of embryos to sort through.  The big question is: how many embryos is enough?  This question has not been answered yet in regards to blastocyst biopsies.

What we should say is that PGS increases the chance of pregnancy per embryo transferred.

All the Best!!

Julio E. Pabon, M.D., F.A.C.O.G.

Medical and Laboratory Director

Fertility Center and Applied Genetics of Florida

Assistant Clinical  Professor

Florida State Univ. College of Medicine

Microscope Stage with Micromanipulators
Copyright J. Pabon collection

Preimplantation Genetic Screening

Preimplantation genetic screening refers to the test that evaluates embryos for the presence of the normal number of chromosomes.  Preimplantation genetic diagnosis refers to the testing of embryos for the presence of a known disease that is carried by the family.  Whether clinics should offer PGS to all IVF patients is a very good question.  The answer to that question has changed recently.  In the past, the past being early 2012, we were still testing our embryos on the third day of “in vitro” growth.  We had been doing embryo biopsies for the past 12 years and offering the highest technology available.  All of our patients understood that the biopsy of day 3 embryos had the significant limitation of “mosaicism.”  That is, there was a 7-10% chance that the single cell that was tested would not represent the “inner cell mass” that would develop into the baby.

A cell or blastomere being removed from a day 3 embryo
Copyright: J. Pabon collection

Recently, after more scientific information became available and the techniques for the biopsies of blastocysts were improved, we realized that the biopsy of blastocysts would be less invasive to the embryo than a day 3 biopsy and that the reading of more than one cell would provide our reference labs with more DNA for testing and therefore a higher veracity of the results.  Dr. Pabon met with Dr. Hughes from Genesis Genetics during a congress in Austin, Texas in May 2012.  At that meeting, Dr. Hughes shared much recent information regarding increased accuracy of pre-implantation genetic screening and diagnosis when several trophectoderm cells were  submitted for analysis.  It is estimated that the results of trophectoderm biopsies are more than 98% accurate.

Laser Assisted Hatching
Copyright J. Pabon collection

The accuracy of the genetic tests of embryos based on the biopsy of the trophectoderm are demonstrated by the pregnancy rate in excess of 80% when a single embryo tested in this way is implanted.  By comparison, embryos that were biopsied on the third day, did not have as high an implantation rate.  This most likely was due to limitations due to mosaic embryos, but also may have been due to the actual biopsy process of a day three embryo.

A hatching blastocyst just prior to laser biopsy
copyright J. Pabon Collection

So, if a physician can transfer a single embryo and enjoy a chance of pregnancy in excess of 80%, this means that the technology is more accurate than before and also that there is no need to transfer more than one embryo.  That means that blastocyst biopsies may revolutionize IVF by allowing more single embryo transfers with a very high chance of pregnancy.

The table below shows typical results of trophectoderm blastocyst biopsies.  “Euploid” is a genetic term that refers to the normal number of chromosomes.  The X and Y chromosomes indicate the gender of the embryo as XX female or XY male.

Report from a blastocyst trophectoderm biopsy from Genesis Genetics after trophectoderm laser assisted blastocyst biopsies.

Dr. Pabon after surgery in 2012
copyright J. Pabon collection

By: Julio E. Pabon, M.D., F.A.C.O.G

C.E.O.

Fertility Center and Applied Genetics of Florida / www.geneticsandfertility.com

Assistant Clinical Professor/Florida State Univ. College of Medicine

Sarasota / Bonita Springs, Florida