- Age and Fertility
- CDC Report on Fertility Clinic IVF Success Rates
- Chromosomal Abnormalities in Eggs
- Donor Eggs
- Egg Banking
- Egg Donation
- Egg Donation Cost
- Egg Freezing
- Egg quality
- Embryo freezing
- Embryo implantation
- Fertility Preservation
- Frozen embryo transfer
- IVF Clinic Success Rates
- IVF Cost
- IVF Poor Responders
- IVF success rates
- Low ovarian reserve
- Micro IVF
- Mild IVF
- Mini IVF
- Minimal Stimulation IVF
- Number of IVF Embryos to Transfer
- Oocyte Cryopreservation
- Ovarian Reserve
- Ovarian Reserve Tests
- Preimplantation Genetic Screening
- Single Embryo Transfer
Fertility, IVF and Egg Donation
Ideal treatment of the poor responder for in vitro fertilization is problematic. Over time, I see more and more patients that have failed multiple IVF attempts at other clinics. The majority of these patients fit into the poor responder category.
Generally, the poor responders should be identified by the fertility doctors before starting an IVF cycle. At our fertility clinic we use ovarian reserve testing to evaluate a woman’s expected response to the stimulating medications. As our basic ovarian reserve screening, we do:
- Antral follicle counts by ultrasound
- Anti-mullerian hormone (AMH) blood tests
- Day 3 FSH, LH and estradiol blood tests
These tests will identify the vast majority of poor responders before they get to an IVF attempt. Identifying the problem in advance allows us an opportunity to do something to improve the response (and the outcome) with the first IVF attempt.
The definition of a poor responder is variable. Regardless of the definition one uses, the basic idea is that poor responders do not respond well to the IVF ovarian stimulation protocol by making a good number of mature follicles. Less mature follicles means less eggs retrieved which results in lower numbers of embryos and less chance to have one that is a “marathon runner” (baby).
For example, women under 35 years old give an average of 12 eggs with IVF. However, poor responders would only produce about 1 to 6 eggs. The chances for success with IVF are very much dependent on two variables – the quantity and the quality of the eggs.
Therefore, if we could come up with a treatment that would help the poor responders to give either more eggs or better quality eggs or both, we would be able to positively impact the chance of having a baby.
Various types of supplementation protocols have been used to try to improve outcomes for IVF poor responders. In this article I want to discuss the use of growth hormone for this purpose.
Growth hormone has been used for poor responders for many years. However due to the very high cost of growth hormone in the past it was rarely utilized. However, over the years with more competition in the pharmaceutical marketplace the cost of growth hormone has come down. During this same time frame, more studies have been published showing benefit from treatment with growth hormone for IVF low responders.
20 years ago, growth hormone treatment added about $5000 to the cost of IVF. That was too high. With the drop in the market price for growth hormone the cost has come down to about $1000 currently. This price change has made it more feasible and potentially a cost-effective addition to the IVF stimulation protocol.
Although all of the studies that have investigated this had small sample sizes, several of them showed significantly improved IVF success rates in poor responders that supplement their stimulation with growth hormone. For the most part, the studies all showed the same thing. Adding growth hormone to the ovarian stimulation protocol for poor responders significantly increases the chances for a pregnancy and a live birth.
The mechanism by which growth hormone would improve IVF success rates is not clear. However, based on animal and human studies it has been shown that growth hormone is involved in production of steroid hormones in the ovary and in development of ovarian follicles. Studies have shown that if mice are lacking the growth hormone receptor and growth hormone binding protein there is a significant reduction in the development of ovarian follicles.
It is also thought the growth hormone could increase the production of insulin-like growth factor 1 (IGF-1) in the ovaries. IGF-I is thought to be involved in regulating follicle development, estrogen hormone production and maturation of eggs.
Several studies have shown improved IVF live birth success rates after supplementation of growth hormone in poor responders. Although the success rates are still not as high as seen in normal responders to stimulation, they are significantly improved over the baseline success rates expected in poor responders.
For this reason, I have been using growth hormone supplementation for many of my poor responding IVF patients. Whether the additional cost of the growth hormone supplementation is worth it is a more difficult question.
Of course, if we knew that the growth hormone would get the patient to a successful pregnancy and a live birth – it would be a no-brainer. However, this is not magic and many women who use growth hormone supplementation will still have unsuccessful IVF attempts.
Some couples will move on to egg donation because of the high success rates with donor eggs instead of continuing to attempt low-yield IVF with their own eggs.
The most effective dosage and duration of growth hormone has not been clarified yet. The published studies have used:
- Doses between 4mg – 24mg, given daily or every other day
- Used it for the first several days of stimulation, or for the entire stimulation phase
Poor ovarian response to stimulation is a difficult problem without a perfect solution at this time. Supplementation with growth hormone is one way we can try to improve the odds for poor responders.
Larger randomized controlled trials are needed to figure out how much improvement in outcome we can expect by using growth hormone as well as which subgroups of patients could benefit the most.
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.
Welcome to the
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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