Laura Garcia de Miguel, MD
Medical Director at Clinica Tambre, Clinica Tambre
Category:
Male Factor, Success Rates
Watch the video recording of the live #IVFWEBINAR with Dr Laura García de Miguel, a Medical Director at Clínica Tambre in Madrid, Spain, who discussed the male factor and its impact on successful IVF treatment.
Dr Laura García started by explaining all the steps each patient goes through to get a proper diagnosis. All patients start with the first appointment with one of the fertility experts, and then they have a diverse diagnostic test, and if necessary, the appointment is scheduled with the urologist.
Dr García added that before the first consultation, it’s recommended to do the sperm analysis, and then freezing the sperm. The treatment option will be chosen, depending on the patient history and sperm analysis result. After that, the team will indicate additional tests that might be required. All the treatments that can improve the male factor, such as antioxidants, are always explained during consultations, and as always, if it is necessary, additional urology consultation will be offered.
During urologist consultation, we will take care of severe cases of male factor. We will have the possibility to do a testicular scan to exclude pathology that could cause problems. Also, we can organize the testicular biopsy if necessary.
Dr García explained that at Clínica Tambre lab, there is a possibility to offer various treatment options and perform several tests, such as:
When performing sperm analysis, we will consider general aspects such as pH, colour, viscosity. We will also study concentration, motility analysis and also morphology.
Regarding concentration and motility, these two parameters are very important. Normal sperm analysis means that there is at least 15 million per millilitre of spermatozoa. With the type of micro zoom we use, we will study the concentration. There is always variability, there is no male who would have the same parameters, in different samples or spermiograms.
It’s very important to understand that concentration is one of the main parameters to understand male fertility. Regarding motility, the biologist will study the type of abnormality these men have. We need to study the movement, there is type A, which is the most progressive motility. Type B means that the movement is reduced, type C, means that sperm is totally non‑motile.
Regarding morphology, the normal range is to have at least 4% of normal spermatozoa. Dr García mentioned that she has a lot of patients telling her that they only have a 5% of normal spermatozoa, and they think this is very bad, the truth is this is not a problem because there are millions and millions of sperm in the sample.
The majority of sperm is abnormal. For example, there are some head defects, or acrosomeless, which means that this spermatozoon does not have the chromosome part. There can also be midpiece defects in the neck or tail defects.
The normal parameters regarding volume, it’s at least 1.5 millilitres. The total sperm count is at least 39 million and a concentration minimum of 15 million millilitres. If we consider the whole motility, it’s 40%, but if we focus on progressive motility, spermatozoa type A and B, it needs to be at least 32%. There should be at least 58% of vital sperm, and sperm morphology should be 4%. pH should be more than 7.2, and peroxidase-positive leukocyte levels should be less than 1 million per millilitre.
In the spermiogram, it’s very important to confirm recovery sperm number during swim-up and sperm survival after 24 hours. Based on that, we will consider the specific treatment for your case. If we have more than 6 million per millilitre, even if there are problems with motility, we can indicate IUI. If we have 3 to 6 million per millilitre, we will go down directly for in vitro fertilization, we can do the classic in vitro fertilization. By contrast, if there are less than 3 million spermatozoa per millilitre, we need to go directly to ICSI, which is an Intracytoplasmic sperm injection.
If the results of the spermiogram are altered, it must be repeated. The following aspects need to be evaluated because they could interfere with the results. The sample collection time is crucial, we always recommend to all our patients to leave the sample at our clinic. The soonest the sample enters the laboratory, the better. The loss of some fraction also needs to be reported to biologists, sexual abstinence is also very important to consider because if we have more than 3 days of sexual abstinence, it could cause problems, but if we have long sexual abstinence, such as two weeks, that will create problems. It is also necessary to ask for the ejaculation frequency of the patient, the last fever periods because if someone had a fever for a long time within those 3 months before providing that sample, it could interfere. The intake of medicines in that previous time of 3 months and the current occupation can also impact the spermatozoa.
Comet fertility is a test that allows us to evaluate the percentage of fragmented sperm in the ejaculate. There are two types of fragmentation that we need to consider. First is the simple strand fragmentation, and the second, double-strand fragmentation. The simple strand fragmentation needs to be studied when failed IVF cycles occur, and there is impaired correct fertilization.
The double-strand fragmentation is indicated when there are recurrent miscarriages, failed IVF cycles and poor embryo quality.
Comet fertility can also be studied in a first cycle without previous failures, but when there is a low concentration and low motility, mainly when we have less than 10 or 5 million per millilitre. Also, when motility is less than 25% and in cases of long infertility that lasts many years and when the man reports that he is a smoker or has a high intake of alcohol or takes more than 2 cups of coffee or tea per day.
It’s the genetic test performed on spermatozoa. Chromosperm test allows us to evaluate the chromosomal content of the sperm in an ejaculate. It is a fast and effective way of detecting general chromosomal alterations that could affect the treatment success rate.
Even if the karyotype test is normal, but a male factor is involved, the Chromosperm test will be recommended.
It is indicated to perform it when leukospermia is present, so there are more than 6 leukocytes per 40x fields. When there is severe asthenospermia, so there is less than 20% of sperm motility, sperm agglutination or hypospermia, which means less than 1.5 millilitres volume.
Also, it’s very frequent to have infections in the genitourinary tract, in the Oligoasthenozoospermia problem.
It’s always necessary to have 3 samples: the first urine, the second part of the urine and the semen in the last part. It’s very important to identify if the infection is the cause of Oligoasthenozoospermia. When we identify the problem, we have many patients who have an infection, and after treatment, they improve their results a lot, it’s always recommended to use antibiotics for 3 weeks and then repeat the test and confirm that the infection is no longer there.
Sometimes there are repeated prostatitis, so it means that after the first round of antibiotics, the results are not better, and we need to do more and more rounds of antibiotics. Sometimes we need to offer different antibiotics and then freeze the sperm after washing because sometimes it’s very difficult to get a sperm without infection.
It is a magnificent technique to improve the results for a man having abnormal Comet results.
When the simple strand DNA fragmentation is altered, it is normally treated with antioxidants for 3 months, and usually, it can improve the semen quite a lot. Usually, Coenzyme Q10, gluten, zinc, magnesium, etc., are recommended. When double-strand DNA fragmentation is altered, FertileChip can be used to select sperm.
If the results of the double-strand are less than 60%, it’s normal. If it is between 60 and 80% of fragmentation, we recommend using FertileChip, and we have good results with this technique. If there is more than 80% of fragmentation, we need to decrease that fragmentation, and we do recommend taking Curcuma piperina for 3 months, and if after 3 months it is still very high, then we should consider sperm donation or genetic screening of the embryos because, with more than 80% of fragmentation, the FerileChip won’t provide good results. Dr García emphasized that it’s very important to remember that when using FertileChip, it’s always recommended using a fresh sample.
If the sperm has a very low quality, there were different failures, or if there is azoospermia, we can always use our sperm donor bank. At Clínica Tambre, there is an extensive donor selection process, and Fenomatch technology is used to select the best donor for you. As Dr García mentioned Clínica Tambre has the oldest sperm bank in Madrid, and it’s one of the oldest in Spain.
It’s always recommended doing karyotype for everybody who is having problems with fertility. However, it’s always obligatory if there is a male factor involved. It is done by a blood test, where we will exclude translocations and other genetic problems. A normal male karyotype is written 46, XY. If there is any abnormality in the karyotype, we will indicate PGS. A biopsy of your embryos will be done to confirm the normal embryos in terms of chromosomes, and we will exclude the abnormal ones.
Some other tests can also be indicated for the male factor: FSH, LH, testosterone hormone test. We can also indicate to do the Y chromosome microdeletion test, which is also a blood test. Chromosomic microdeletion (YMC) is a family of genetic disorders caused by missing gene(s) in the Y chromosome. Many men with YMC exhibit no symptoms and lead normal lives. However, YMC is also known to be present in a significant number of men with reduced fertility.
We can indicate to perform a test for cystic fibrosis. Most men with cystic fibrosis, about 98%, are infertile because of an absence of the sperm canal known as the congenital bilateral absence of the vas deferens (CBAVD).
IUI is indicated only in very good prognostic cases. The sperm needs to have a recovery of more than 6 million per millilitre. It’s indicated in young women with a short infertility time and will be recommended in no more than 3 to 6 cycles. In IUI, female ovaries are stimulated and then when the follicle or follicles are ready, we will collect the partner’s sperm sample, we will concentrate it and insert the sperm in the uterus. The sperm needs to be washed and needs to run in the tube, find the egg and fertilize. The embryo will implant in the uterus directly. This technique is only indicated if we have a very good prognosis with no severe male factor.
If we have at least 3 to 6 million spermatozoa per millilitre, we can perform a classic IVF. Once the eggs are obtained during the egg retrieval, we will put them in the culture media with a drop of sperm, and the best spermatozoa will fertilize the egg naturally.
There is also a possibility to do IVF in total. All the eggs will be fertilized with a classic IVF. There is also an option for IVF in 50%, and ICSI in other 50% if we are not sure that this particular patient can have a good prognosis with total IVF. This natural process compared to ICSI has better neonatal outcomes than ICSI.
ICSI is the main treatment we would recommend for male factors, and it is an artificial selection of spermatozoa. We will have around 80% of fertilization rates, and of course, it’s obligatory if you have Oligoasthenoteratozoospermia (OAT).
The preimplantation genetic screening will be done after the in vitro process. It will be recommended when there are abnormal karyotypes, either in men or women, or if the Chromosperm test result is abnormal, or the Comet test result is very high.
The embryo will be biopsied, we will study some cells of the external part of the embryo and will confirm which embryos are having normal chromosomes and which are abnormal and need to be excluded from embryo transfers.
Azoospermia can be caused by secretory or obstructive problems. Secretory means that there is no production of spermatozoa, and if it is obstructive, it means that there is an obstruction in the seminal conduct. We could go to the testis and do a testicular biopsy.
In such cases, it’s very important to consider the parameters in the spermiogram. We need to consider volume, pH and biochemistry.
A Maltase of less than 20 is obstruction of the epididymis, and then we need to do a testicular biopsy, and we need to do ICSI.
By contrast, if we have hypospermia, a low pH, less than 7 and low fructose, it means that there is agenesis of ducts or vesicles. We need to check the cystic fibrosis. If there is a negative result, the man does not have cystic fibrosis, we can do a testicular biopsy with ICSI. If the problem of cystic fibrosis exists, then we need to do a testicular biopsy and a genetic screening of the embryos.
If we have a low volume with leukospermia, phosphatase and citric acid, it means there is an infection. Therefore, we need to do a semen and urine culture and recommend treatment with antibiotics. If the semen and urine culture is negative, we should do a testicular biopsy.
If volume, pH and biochemistry are normal, then we need to test Y chromosome microdeletion, and if that is the problem, we should do a testicular biopsy and genetic screening. If there is no such problem, we need to do FSH and LH hormones. Low levels of these hormones suggest hypogonadotropic hypogonadism. We need to use gonadotropins injections to try to make the function of the testicles come back to normal. If the FSH and LH levels are high, we should do the testicular biopsy and consider performing the ICSI procedure.
Y chromosome deletions are not always linked with azoospermia. There are 3 phenotypes with clinical relevance.
It all depends on the type of microdeletion, if it is the AZFa, AZFb, it is necessary to go directly for sperm donation. If it is the microdeletion AZFc, if there are spermatozoa in the sperm, then we can do the ICSI procedure. During the genetic counselling, we’ll need to explain to the couple that this problem could be transmitted to their sons. This could mean they could also be infertile due to that issue.
Dr García concluded that it is very important to study in deep every case. Treatment counselling and pregnancy rates are extremely important to inform the couple in particular, and only in azoospermia or very severe Oligoasthenoteratozoospermia (OAT), a sperm donor will be indicated.
It really depends on each problem. As I said before if the problem is fragmentation, single strain then antioxidants are recommended, and if the problem is with a double fragmentation, the recommendation is curcumin. If you want to do the mix of antioxidants and curcumin, it’s fine, so whatever antioxidants such as coenzyme Q10 and magnesium, zinc will improve it. There are usually multivitamins that you can buy directly in the pharmacy that is vitamins specific for a male factor.
My recommendation is that if he has children, it’s not necessary to do the karyotype, it is recommended, only if after or before the children were born there were miscarriages. Regarding the poor morphology and poor DNA fragmentation, if there is a very low morphology, it could be abnormal DNA fragmentation, but I have lots of patients having abnormal morphology and then when we do the DNA fragmentation everything is absolutely fine. It’s not necessarily linked.
If we have different failures, it’s always necessary to remember that the embryos because of the male factor or because of the eggs could be abnormal. We have to do the PGS and also I would recommend starting doing implantation failure check. If you have had different blastocyst transfers with good morphology, not only do the genetic screening but also do the implantation failure study such as the window of implantation, hysteroscopy, coagulation disorders, immunological problems etc.
We do the TESE because our urologist considers it has the best outcome with that, so we don’t have the micro TESE surgery.
Lifestyle is something very important, we do have patients such as for instance drivers that are sitting for a long time, and that could be a problem for the sperm function. We all live in a world that it’s really crazy, having phones and many radiations close to us, so we know this is not positive for the sperm but by contrast, we cannot only consider this is the problem for the male factor. We need to improve our lifestyle, so no smoking, having a very good diet with a lot of fruit and vegetables, fish and also consider taking vitamins and these types of species like Curcuma but yes we cannot only focus on the radiation problems
Yes, I think we really focus a lot on the eggs and the women and the age but sometimes we don’t spend enough time to study the male facto, so I completely agree with you.
It’s not only the low testosterone that really is the cause of the sperm count, but we also need to do all the tests that I recommended before mainly FSH, LH regarding the parameters in the spermogram and see if finally, it is because hormones are low, so FSH, LG and testosterone, then treatment would be gonadotropins to improve the count of the sperm. In case there is a very severe Oligo-, Asthenic-, Teratospermia or azoospermia by contrast if there are more than one million millilitres then it’s not necessary to do that and we just go directly with ICSI procedure.
With normal volume and PH we need to do all the tests I’ve mentioned before, so karyotype, why microdeletions, the cystic fibrosis and very important to talk with urologists to understand what is the problem and if we can go to the testicle because it is an obstructive problem, and we can retrieve spermatozoa from the testis or not.
Yes, it could be one of the problems if there is an infection, some of the infections, for instance, ureaplasma could really cause repetitive miscarriage. There is a problem that your embryos are already frozen and with the frozen embryo, it’s not really recommended to do the genetic screening because it’s an invasive procedure and with frozen embryos, it does not really work very well. You also need to do the repeated miscarriages tests to understand where the problem is and if everything is clear and you don’t have problems in the uterus, in your coagulation, with your immunity, then you need to talk with your clinic. It’s important to check if it is more convenient to do the transfer directly or if by contrast, they would recommend another round with more embryos do the genetic screening on all of the embryos.
The latest studies show that it’s around 3 days. I would say 2-3 days is the best, between 2 and 4 days, 1 day is a very short time, so usually, concentration could be decreased, so at least 2 days of abstinence and no more than 4 days.
Yes, we consider fragmentation could be decreased when there is a shorter time of abstinence for instance in the Fertile Chip sometimes we ask for 2 samples the same day, so yes with short abstinence it could be reduced.
There is no evidence that sperm count could be improved with exercises, so of course, fragmentation and all the quality inside could be improved if we change our lifestyle, but not the sperm count.
Yes, absolutely we can work with that sample, but it’s really necessary to go directly to the ICSI procedure. I wouldn’t recommend other treatments in your case, and also it looks that you should have changed in your sperm parameters, so perhaps it could be important to exclude infection and do sperm and urine culture.
We do understand that the specific work of the sperm in the embryo starts from day-3. But it does not mean that if there is a blastocyst even of good morphology reaching day-5, that everything is okay with the sperm. It could be also abnormalities inside the sperm, such as abnormal fragmentation or chromosome disorders that could interfere in the genetic charge of that embryo.
So, 50% of embryos are not evolutive from day-3 but depending on each case if all the embryos have good development till day-3, and then, by contrast, there isn’t any embryo achieving day-5, yes we need to study more in-depth the sperm to exclude problems with fragmentation for instance.
Mainly for necrozoospermia what we need to exclude is infections. If the cause is an infection, it will be improved after antioxidants. By contrast, if it is not the cause, then there’s nothing to do only antioxidants, but of course, although it’s not a good parameter, it’s not a positive parameter if concentration and mobility are good and we do ICSI procedure, the results are going to be good.
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