Low Ovarian Reserve, Age and IVF
Does low ovarian reserve mean early menopause? Is it always connected with age? Can it be reversed? What is the best fertility treatment for low ovarian reserve? What are my chances of pregnancy with low ovarian reserve? Find out the answers to these questions from our live webinar “IVF with donor eggs, low ovarian reserve and age – Patient Case Study” presented by dr Laura Villar Torres, a gynecologist specialized in Reproductive Medicine.
It’s widely understood that increased age and decreased ovarian reserve are linked, but can one be a factor of failure to conceive without the other, and what options are available to women who are dealing with age-related infertility, or have been diagnosed with a low ovarian reserve?
In this webinar, Dr Laura Villar Torres, a gynaecologist specialising in reproductive medicine, in the reproduction unit, Mexico, discusses the case study of a 44-year-old woman trying to conceive, via IVF, and looks into the issues, testing and treatments for patients wanting to a child, but whose reserve is diminished.
Ovarian reserve is defined as the quality and number of remaining follicles and oocytes (eggs) of the ovaries, at any given time, it’s a measure of how well the ovaries are functioning.
It’s very much recognised that an increased maternal chronological age does decrease female fertility, but why is this?
Women are born with their total number of eggs and oocytes do not regenerate. On average, during the fourth month of foetal development, females will have between six to seven million oocytes. A rapid loss, of eggs, is experienced at birth, when the total number decreases to between one to two million; this birth figure is classed as 100% of a woman’s oocytes. When menarche (the first occurrence of menstruation) is reached, this figure drops to around 300 – 400,000, 23% of the amount at birth. This further reduces to 12% (180,000) at age 30, and then again to 45,000, or just 3%, around the 40-year mark, continuously diminishing as a woman heads towards the menopause.
Whilst it’s known that reproductive decline does occur with age, external factors also play a role in influencing the quality and quantity of a woman’s eggs. Genetics, environmental factors and medical history, such as endometriosis, autoimmune disorders and treatments for cancer, just to name a few, can have a negative impact on fertility. However, from data, it appears as though age, over low ovarian reserve through other factors, has more ability to affect reproduction, when a woman uses her own eggs.
So just how can ovarian reserve be measured and is it something which has symptoms that can be recognised?
Dr Villar Torres explains how important it is to understand that a poor, or low, ovarian reserve test result does not constitute an absolute inability to conceive, and that alone should not be the sole criteria with which to limit, or deny, fertility treatment.
Ovarian reserve testing usually falls into four categories which are: Clinical, where age and menstrual cycle characteristics are taken into account; Biochemical, including the measuring of FSH (Follicle-stimulating hormone) and AMH (Anti-Mullerian hormone) levels; antra follicle count, ovarian volume and blood flow tests, via an ultrasound and, finally, dynamic testing, such as gonadotrophin agonist stimulation and/or FSH ovarian response investigations. Dr Villar Torres advises the different methods of testing should be combined in order to get the clearest understanding of each individual woman’s ovarian reserve.
Various protocols have been designed to assist patients with diminished quality and/or quantity, including the administering of fertility medications, however, Dr Villar Torres points out that it is incredibly difficult to judge how a woman will respond to these, based simply on her ovarian reserve markers, and advises that women should be offered the chance to try differing regimens of ovarian stimulation. If these medications are not shown to make a difference, or if the ovaries still don’t respond, then there are other options, such as assisted hatching or donation. Oocyte and /or embryo donation is now an established standard of practice, for the treatment of age-related infertility, and is associated with higher rates of pregnancy success; egg donation reverses the age-related decline in embryo quality and subsequent implantation, increasing live birth rates, in women post 40.
When looking at the case study of a 44-year-old female trying to conceive, having gone through three unsuccessful IVF attempts, using her own eggs, Dr Villar Torres discusses the variation of medication and procedures used, noting some improvement. However, no cycles, for this patient, resulted in a pregnancy, until donor oocytes were used; the patient is now 34 weeks pregnant.
What do the chances of pregnancy look like then, for women with increased age or low ovarian reserve?
Dr Villar Torres is keen to point out that it really does depend on all of the specific factors. Every patient, and case, is individual, and each woman will have a differing number of oocytes, of varying quality. She also advises clients that it’s important to understand IVF is an assisted reproduction treatment (ART) and science, and that not all practitioners will necessarily agree on the same strategies. However, whichever regimens or protocols clinics decide to use, they must always remember that each woman is unique, therefore personalisation of treatment, in whatever form, always has the capacity to optimise reproductive outcomes.
Questions and Answers from the event
How many times is the stimulation of an egg donor allowed in Mexico?
We are guided by the guidelines issued by Mexican experts on infertility, but the law has not yet been formalized and the official standard in Mexico is in development. Although, technically there are no restrictions here in Mexico, sometimes we follow the example of other countries like Spain, where there is a limit of six live newborns; so when there are six children born from the oocytes that you have donated, you will not be able to donate again.
Why only 3 times of stimulation? Is it harmful to their ovarian reserve for their future fertility? What is the reason? Or harmful for their health? Are there any studies?
It is not only three times; it depends on how many newborns we have of the same oocytes. We have a limit in egg donation of six live newborns. Also, egg donation is not risky. It cannot cause any harm to the donor. It is a process in which the donor receives hormonal stimulation to provoke ovarian production and moderation and then a follicular puncture in which the oocytes are extracted. However, this is performed under anaesthesia and the main issues are associated with that. As for the stimulation, there is a risk of Ovarian Hyperstimulation Syndrome, but this is unlikely, due to the ultrasound and the analytical controls that the donor would have to undergo during the process. Egg donation does not affect the donor’s own fertility as the oocytes obtained are oocytes that, in principle, would degenerate anyway. We do not take away the potential of being a mother.
I’m 38. My AFC is 11, AMH was about 8. I’ve had two failed IVFs with my own eggs. Should I move to donor eggs or should I try one or two more IVFs with my own eggs?
It could be important to analyse your case to know if all the factors required to favour a good result were analysed with the purpose of being able to give a better prognosis with your own oocytes. However, here, your age plays an important role in oocyte quality and there is an advantage in using donor eggs.
How early can low ovarian reserve be discovered?
The most fertile period for a woman ranges from 16 to 30 years of age and in that time she has a good quantity and quality of oocytes. From 35 to 37 years of age, there is a significant decline in the ovarian reserve. So we can determine your ovarian reserve with a specific blood test and an ultrasound at any time. Any woman can have this test done at any age to check her ovarian reserve.
Can an AMH test be done without the approval of the patient?
No. This cannot be done without approval. Knowing the result is, however, crucial before you begin infertility treatment. The AMH has been established as the best prognostic marker for ovarian response during the cycle, in fertilization and in IVF but, no, it cannot be done without your approval.
What is the percentage of error in conducting the AMH test?
It depends on the laboratory but we can say that the detection limit or detection range can vary from 0.6 ng/ml to 1ng/ml. It’s important to check follicles and correlate it to AMH level.
Regarding the AMH, FSH and other required tests, I have noticed that labs have different requirements prior to conducting the test. Which one is true?
Sometimes you need to do these on a specific day of your cycle, but usually, you can do the tests at any time. It is important to know which test the gynaecologist has asked you to do. This doesn’t change with the laboratory. Most of them have the same requirements, for example, at least 8 hours fasting in the first 2 or 5 days of your cycle, but that’s all.
How can one verify the clinic and the doctor’s experience in the field? How to verify if the IVF lab is accredited?
The most important thing that you can research, as obviously there are so many clinics in Mexico, is their results. It is important to find out about the results so that you can have confidence. It is important to ask for a first meeting, and many of these are for free, to talk with them and analyse your case. This would be good advice.
I’m 42. I have had eight IVF cycles. Three of them were with donor eggs. All these failed. Two mechanical pregnancies. Could it still work if I try again with donor eggs?
It could work but there are so many other factors, for example, the endometrium and the implantation. There might be something wrong with here so maybe this is one of the reasons you haven’t had a successful pregnancy. You could try again and maybe be successful on your next cycle, but you should check those factors first. It is important to have a hysteroscopy, to check your cavity, your uterus, and maybe if there is a growth it would be good to know if the problem was there. It would be good to have this before your next IVF cycle.
What is the age limit for IVF for women in Mexico?
This depends. The age limit for IVF in Mexico for treatment with your own eggs is 45 years old. However, this is not a specific legal age limit. The limit also depends on your ovarian reserve and some other factors which would need to be checked. We also recommend donor eggs up to 45 years old. So the age limit for IVF either with your own eggs for with donor eggs it’s 45.
Do you recommend high or low stimulation for a woman with low ovarian reserve? (I’m 44 and normally I had two oocytes after stimulation, regular cycle).
It is true that we use high stimulation because we believe we can retrieve more oocytes but the low treatment is cheaper and we have the same or similar chances of pregnancy. The advantage of doing the minimum stimulation is the lower cost at the end but the results are almost the same; you have the same chances of pregnancy.
I’m 46. Can I use donor eggs since I have already tried with my own eggs before and that wasn’t as successful as I hoped?
Yes, you can use donor eggs. Maybe this is because of your age, and as we already said, age is the most important factor in low-quality oocytes, but it is important to check this in your specific case.
My husband is 35, non-smoker, husband’s sperm results: morphology, shape normal, 1.8%. Does this affect conception? The other results are: concentration is 184 mln, motility +B is 51%, DNA fragment is 46%. Do we need to go with some special treatment or is it okay for us to conceive naturally with these sperm results?
Your husband’s sperm sample results are salutary in morphology, but DNA fragmentation above 30% is not normal, and your husband level is 46%. We know that sperm DNA fragmentation is increasingly suggested as an infertility predictive factor. Most of the studies into the association between DNA damage and lower fertilization, impaired embryos or higher miscarriage rates agree with this. I would recommend an IVF cycle with ICSI because the selection of the spermatozoid could improve pregnancy outcomes.
I’m 41 and still ovulate. Ovulation test strips aren’t working on me. My cycles are always on time. How to find out those 48 hours of ovulation?
We would need to know why the strips aren’t working. Sometimes we have specific characteristics of the cervical mucus. It would be a little difficult to explain it here, but you could go to your gynaecologist and they could explain it better.
Do you recommend high or low dose stimulation for a woman with low ovarian reserve? Are there any critical studies about success rate with only eggs? (I’m 44, no IVF until now, regular cycle, very low AMH, two oocytes before stimulation).
As I said before, high or low stimulation will give the same results.
Can a woman with low ovarian reserve conceive naturally?
Women with a lower varying reserve can conceive naturally. It a very low percent, less than 5%, but it can happen.
How can we improve egg quality?
This is a very good question but it’s also a difficult question. We cannot improve egg quality with a specific substance. There have been a lot of studies but none of them has recommended something that could work. The only real factor to know that we have a good quality egg is the age of the patient. You could take vitamins but this has not been proved to work for all women but it can help with the ageing of the eggs.
What are the chances, if any, of the ovaries being damage during IVF or egg retrieval?
It is difficult to damage the oocytes during this procedure. The procedure is not risky, the chance of complications this very low, less than 5 or 8%, so don’t worry, it doesn’t happen. It is a routine procedure for doctors, of course not for patients.
Are there any prospects for pregnancy for a 29-year-old woman with early menopause symptoms, low AMH? What are your recommendations for treatment?
It is important to know what your AMH is. I would need to know what your andral follicle count is, but you could have a good pregnancy rate with an egg donor. You could try with your own eggs but we have to try first with an ovarian stimulation phase. It is difficult to have a good response in this situation, but you could try one cycle.
Is there any treatment besides IVF/egg donation/IUI that could help younger women with low ovarian reserve conceived naturally if the cause of the lack of pregnancy is not menopausal but unexplained?
This is very difficult if you want to conceive naturally because we only have about a 5% success rate. There is no help that we can give for you to conceive naturally but we can help you with reproductive techniques like IVF. We can try one cycle with your own eggs and if this doesn’t work we can go for an egg donation. Of course, these suggestions are all kinds of fertility treatments. We have to say that egg donation treatment is highly successful and is a good option if you were willing to consider it.
Does acupuncture help before egg donation?
We don’t have good studies to help me answer that question. It could work if you are comfortable with it. The important thing is that you don’t change the treatment that we give you, but if acupuncture works for you, if it helps you lower your stress levels, it’s okay. It’s definitely not harmful.
What’s the importance of FISH (fluorescence in-situ-hybridisation) and Karyotype test?
These are very important tests. FISH is a test that we do on the sperm, where we analyse its DNA and it’s a good technique to see how good the genetic information is. We analyse some of the chromosomes that can tell us if there is any damage there.
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