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Fertility, IVF and Egg Donation
by Dr. Mohamad Irani on Apr.02, 2019, under Chromosomal Abnormalities in Eggs, Embryo implantation, IVF success rates, Miscarriage, Number of IVF Embryos to Transfer, Preimplantation Genetic Screening, Single Embryo Transfer
It has been an exciting time for the field of Reproductive Medicine, which has witnessed major advances over the last three decades. For instance, the recent evolution in Preimplantation Genetic Testing for aneuploidy (PGT-A, formerly called Preimplantation Genetic Screening [PGS]), has provided an important tool to enhance embryo selection and subsequently elective single embryo transfer (eSET).
Advancements of Preimplantation Genetic Testing for Aneuploidy (PGT-A)
Embryo biopsy on Day 3 has been suggested to adversely affect the implantation potential of the embryo. Hence, the majority of IVF laboratories have switched to blastocyst biopsy on Day 5 or 6. Evidence supports that the improvements in the biopsy technique, and the removal of approximately 4-5 cells from the trophectoderm (precursors to the placenta) on Day 5, when performed by expert embryologists, may not negatively impact the reproductive potential of the embryo.
Furthermore, enhancements to genetic testing, which currently analyzes all chromosomes compared to the initial platform that analyzed only a limited number of chromosomes, have significantly improved the accuracy of the test.
Clinical Benefits of PGT-A
This technology has significantly decreased miscarriage rates and increased the implantation rate per transfer. The high implantation potential of embryos determined to be euploid by PGT-A has contributed to the increased adoption of elective single embryo transfer, (eSET). This has subsequently reduced the incidence of multiple gestations, and all associated maternal and fetal complications.
Despite its critical advantages, PGT-A comes with some risks and may not be the best option for all patients; therefore, personalization of care is key to success. All patients should understand the pros and cons of each procedure in order to make informed decisions.
In my practice, I help patients understand the advanced reproductive technologies that offer them their best chance of achieving a healthy baby.
Fertility treatment fads and the internet
I’ve been in this field for 20 years and have seen fads come and go. The information exchange and communication between patients and doctors that the internet provides sometimes fosters proliferation of fads driven by rumors – rather than by science.
When I started practicing medicine in the early 1990’s, infertility patients came to the doctor and expected to be told what to do. They wanted some fertility tests done to find the cause for their infertility and then they wanted either intrauterine insemination treatment or in vitro fertilization, IVF to have their baby. There was no internet so couples could not research medical information on their own.
As the internet evolved, couples got more involved in deciding specifics of their infertility care. Most couples now use the internet to educate themselves about fertility testing and treatment options. I think this is great. However, there is a potential downside. It is difficult to separate the wheat from the chaff. There are many worthless tests and treatments promoted and sold on the internet to anyone with a credit card.
When a study comes out and is published in the medical literature regarding a treatment option that might be beneficial the physicians will learn about the new option if it is potentially viable. Then, additional studies will be done to confirm or refute the results from the initial study. Doctors are used to the fact that one study showing a potential benefit from a new treatment option might not stand the test of time and be supported by additional studies done in other clinics.
However, in our news hungry world a study comes out reporting an interesting potential benefit for a new treatment – someone does a press release and it’s picked up on a news wire. Before long, women are discussing it in the infertility forums and on Facebook and in chat rooms as the new treatment option that everybody should be doing.
Coenzyme Q10 and fertility
I want to discuss coenzyme Q10, which is one of the “treatments” that patients are using on their own (often without input from their doctors) in an effort to improve their fertility potential or to increase chances for IVF success. Coenzyme Q10, often referred to as “Co Q10” is a substance that is needed for basic functioning of cells. It is a source of fuel for the mitochondria – which are organelles inside cells that are “power plants” that convert energy for the cell to use.
Interest in coenzyme Q10 as a supplement to improve fertility was sparked when a report from Canada said fertility in mice was improved when the mice were given Co Q10. The mice that were given coenzyme Q 10 before they were given ovarian stimulation made more follicles and better eggs compared to mice that were not given Co Q10. According to the researchers, the Co Q10 seemed to cause the older mice to produce eggs that functioned more like eggs from younger mice.
This study suggests the possibility of a fertility benefit for women with low ovarian reserve. As far as I know, this mouse study has not been repeated and there are not yet published studies of Co Q10 in women having fertility treatments.
Coenzyme Q-10 and egg quality
We all know the chances for pregnancy decline as female age increases after about 30 years old. We know that the decline has a number of causes, but the main problem is a decline in “egg quality”. Egg quality is an important concept involving several critical factors – none of which we can test or measure. One major component of egg quality involves the chromosomal status of the egg. Eggs from older women are more likely to be chromosomally abnormal than eggs from young women.
The human egg is a very large cell. It can be thought of as a big factory with half of the chromosomal complement of a normal human that is sitting and waiting for a sperm to deliver a very small package containing 23 chromosomes (the other half). When a sperm penetrates an egg and releases its package of 23 chromosomes, the switch to the “egg factory” is turned on and embryo development begins.
The process of firing up the factory and starting normal embryo development requires a lot of energy. Mitochondria are very tiny organelles within cells that generate a lot of the energy that cells need. Human eggs have more mitochondria and mitochondrial DNA than any other cell in the body.
What does any of that have to do with egg quality and fertility?
One theory speculates that part of the problem in older eggs is their decreased mitochondrial energy production. Taking that concept a step further, perhaps eggs could function more effectively and efficiently if something could be done to increase the number or health of the mitochondria in the eggs. Maybe the egg could do a better job of maintaining chromosomal normalcy if it had enough energy reserves.
From this came the logic that using dietary supplements of “mitochondrial nutrients” might improve egg quality.
What is coenzyme Q10?
Coenzyme Q 10, which is also known as ubiquinone, is a vitamin-like substance that is present in most cells. It is an antioxidant (meaning it inhibits the oxidation of other molecules). Sometimes, oxidation reactions produce free radicals which can start chain reactions in cells resulting in damage or cell death. So antioxidants can be good when they terminate the chain reactions before there is damage to the cell.
It is not considered a vitamin because all normal tissues in the body make their own CoQ10 so it does not need to be supplied in the diet. It is mainly present in the mitochondria and is a component of the electron transport chain that is involved in generating energy within cells in the form of ATP. The vast majority of the human body’s energy is produced in this way. Therefore, the high Co Q10 concentrations are found in cells with high energy requirements – heart, liver, kidney, etc.
It has been estimated that the average daily intake of Co Q10 is about 3 to 6 mg per day, which mostly comes from meat consumption. The recommended dosage of Co Q10 supplementation varies greatly. The suggested dose is usually between 50 to 600 mg daily in divided doses.
There is controversy as to what the best dose of CoQ10 is for various medical conditions. It is often given at a dose between 100 mg and 300 mg per day. There is some evidence from studies that is safe at a dose of up to (at least) 1200 mg per day.
Should women with fertility problems take Co Q10?
Physicians are trained to practice evidence-based medicine. What that means is that we want well-controlled studies supporting that a treatment is beneficial before we recommend it. In the case of coenzyme Q 10 we can’t justify its use for improving fertility in women based on existing evidence.
On the other hand, there’s no evidence that there is harm from using Co Q10 and it is unlikely that there would be harm since this enzyme is present in every cell in the body and is produced within cells regardless of whether it is present in the diet or not.
So women have read about it and have taken CoQ10 with the idea that they will produce more eggs with ovarian stimulation for IVF and their eggs will get better and perform like younger eggs.
- Even if it doesn’t help, it’s unlikely to hurt – and CoQ10 is not expensive
- Most fertility doctors (including me) are fine with their patients taking Co Q10 if they want to
- Hopefully, a carefully controlled study will be done and published in the medical literature so we will understand more about any potential benefit of Co Q10 for women with fertility problems.
We know that chromosomal abnormalities in eggs are responsible for fertility problems – particularly when the woman is in her late 30s or 40s.
- An abnormal number of chromosomes is referred to as aneuploidy
- Aneuploidy causes the increased rate of miscarriage with aging
- Aneuploidy is responsible for most of the decline in fertility with advancing age (both with and without IVF)
In recent years research has shown the importance of a structure in the egg called the meiotic spindle. This spindle is involved with aligning chromosome pairs so proper division of pairs can occur during egg maturation.
- As women age they are more likely to have an abnormal spindle apparatus that does not efficiently line up chromosomes prior to division
- This causes a higher likelihood for an unbalanced chromosomal situation in the mature egg – and then in the embryo
A recently published study (referenced below) might help us to understand why some women have more chromosomally abnormal eggs at a given age. This study was performed in mice, but may well have relevance for human reproduction as well (in many ways we aren’t as different from mice as we might like). (continue reading…)
Welcome to the
Advanced Fertility Center of Chicago
Richard Sherbahn, MD is a Board Certified Reproductive Endocrinology and Infertility specialist.
Dr. Sherbahn founded the Advanced Fertility Center of Chicago in 1997.
He will post regularly about fertility issues.
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