Genetics & IVF case studies – patients stories

Laura Garcia de Miguel, MD
Fertility Specialist & Medical Director, Clinica Tambre

Genetics PGS / PGT-A, Low Ovarian Reserve, Success Stories

From this video you will find out:
  • Why is it so important to discuss PGS & Carrier Screening test with all patients?
  • What is, (HERES), a Carrier Screening test, and when should it be recommended?
  • Who are the best candidates for the PGT (Preimplantation genetics testing) procedure?
  • Is a natural cycle recommended in cases where the patient got pregnant naturally previously?

When should Preimplantation Genetic Testing (PGT) be recommended?

In this session, Dr Laura García de Miguel, Medical Director at Clinica Tambre, Madrid, Spain, has discussed genetic issues, available treatment options and provided some real-life cases with detailed examination and performed treatment.

Genetics – real IVF patient case

  • a 33-year-old female with normal BMI, no previous IVF cycles, 2 pregnancies, 2 natural pregnancies were terminated

Dr Garcia started with the presentation of the couple with no personal history, no toxic habits, no known allergies, and no previous IVF cycles. As a couple, they had 2 natural pregnancies, one with intrauterine fetal death due to multiple bone malformations, it was induced natural childbirth without complications. The second was also a natural pregnancy that ended in a fatal death at 22 weeks of pregnancy because of multiple bone malformations as well. Then come to the clinic (Clinica Tambre) because they were afraid of a new natural pregnancy, and they have not undergone genetic testing because they have been told that it might be just bad luck with these 2 pregnancies in their home country. They were afraid to go ahead with another pregnancy and risk this happening again. We recommended doing the Genetic Carrier Status Test (HERES) and also the PGT-A to study their embryos. The couple had never done any genetic testing before, they had no genetic counselling.

HERES – The HERES carrier screening offers sequencing of deletion/ duplication analysis for a number of genes (over 300 mutations). We perform this on the female and the male to see if they are carriers of any recessive mutations.

PGT-A – is performed with Next Generation Sequencing (NGS) to read the DNA code of 1 or several genes to determine the genomic sequence of an individual. For each embryo, we are going to test the karyotype with NGS to be sure if they have any chromosomes disorders.

First results

As a result, it was found that both partners are carriers of an autosomal dominant mutation which is glycine substitution in the COL1A1 or COL1A2 gene, which results in a significant defect in the production of type 1 collagen.

Collagen type 1 is a structural component of the extracellular matrix of connective tissue, whose function is to provide support of tensile strength to tissues. This protein is most abundant in bone and skin. This mutation leads to Osteogenesis Imperfecta Syndrome, and that was the cause of the fatal death of both children.

The Osteogenesis Imperfecta Syndrome The Osteogenesis Imperfecta Syndrome is colloquially known as brittle bone disease, and it is a rare disease due to its low incidence. It is 1 every 15000 babies born or even 1 every 20000 newborns that can be affected. It impacts both sexes, races and ethnic groups equally. It comprises a group of diseases caused by a heterogeneous disorder of the connective tissue. It can cause hearing impairment and dental and pulmonary abnormalities.

After learning of this genetic alteration, the couple was advised to proceed with IVF to obtain embryos in the blastocyst stage to carry out the PGT-A. After examing the couple, it was discovered that the female had a low ovarian reserve, and the male partner had asthenozoospermia, as well as a DNA fragmentation of 20%, making it suitable for ICSI (The Intracystoplasmatic Sperm Injection), which is an IVF procedure where a single sperm cell is injected into the cytoplasm of an egg.

Therefore, in this case, because of asthenozoospermia, which means the mobility of the sperm is not in the normal range, it should be at least 32% of mobile sperm, but this man had only 20%. Also, when PGT-A diagnosis is performed, it’s best to do ICSI because we want to exclude other sperm in the external of the embryo, which means that we are more specific in the results of the embryo and do not obtain genetic results of the sperm.

The treatment

As the female had a low ovarian reserve, 2 rounds of IVF/ICSI cycles were done. In the first cycle, 10 stimulation with dual trigger was performed, we got 6 eggs, and 5 were mature and fertilized correctly. We obtained 2 blastocysts, one AB and one BA. PGT-A and PGT-M exams were performed to check for chromosomes problems. PGT-M was performed to exclude babies that were affected with The Osteogenesis Imperfecta Syndrome.

After a month’s break with Yasminelle, other cycles started. We did a dual trigger again, where we use 2 medications to retrieve more mature eggs. We obtained 7 eggs, 6 were mature, 3 were fertilized after ICSI, and again we obtained 2 blastocysts of good morphology, AB and BB. PGT-A and PGT-M have been performed again.


In the first cycle, 1 aneuploid blastocyst was found, which means there was 1 extra chromosome (23), and there was also 1 less chromosome (11), a Monosomy of 11 and a Trisomy of 23. We also obtained 1 euploid blastocyst, it was a healthy embryo. In the second cycle, the result was 2 blastocysts, 1 euploid blastocyst, and the second was aneuploid with a Trisomy 14 and carrier of the mutation.

The first endometrial preparation with Estrogen (Pogenova 6 mg/d) and Progesterone (400 milligrams Utrogestan, every 12 hours, 5 days prior to transfer). The embryo transfer with abdominal scan monitoring was performed, and 11 days later, the pregnancy test was negative.

The couple was very disappointed since they were able to conceive naturally, and now, with IVF/ICSI, it did not work. Therefore, before going ahead with the second embryo transfer, we decided to do EndomeTRIO testing, which is a test that analyses endometrium. As the patient had 2 previous natural pregnancies, we decided to do the endometrial testing in a natural cycle, which means monitoring the ovulation, the follicular development. Once the endometrium was ready, in terms of thickness, and ready to ovulate, we did the trigger for the ovulation with Ovitrel, we added progesterone and did the biopsy.

EndomeTRIO test consists of 3 tests, including the ERA test, to check the window of implantation and be sure what is the ideal moment for the embryo transfer. In this case, it was revealed that it was receptive to LH+7, which means a normal window of implantation. The second test is ALICE to check for infections which were not found. The third test was EMMA revealed dysbiosis, so there was a recommendation to take probiotics.

Before going ahead for the second transfer, we recommended doing treatment of 15 days of vaginal probiotics, for the endometrial preparation, we did a natural cycle using Ovitrel and progesterone 400 milligrams every 12 hours 5 days before transfer. The embryo transfer was done with abdominal scanning, and this time, we had a positive result and ongoing pregnancy that ended in delivery at 40 weeks.


It’s extremely important to talk with patients about Genetic Testing and The Carrier Status test. Plus, a natural cycle for embryo transfer is recommended if previous natural pregnancies have been achieved.

Genetics And Embryo Biopsy – Success Stories
Preimplantation Genetic Testing (PGT) – For Whom, and How Does It Help?


- Questions and Answers

When is PGT-A recommended? Is it recommended in all patients of advanced maternal age? What are the current guidelines?

PGT-A is recommended specifically for women of advanced age, which is considered, depending on studies, 38-40 years. It’s also advised for patients with previous rounds of IVF that were not successful and previous miscarriages. Then, depending on karyotypes and if they are abnormal, we should go ahead with PGT-SR, which is a kind of PGT-A, but it’s used to check if there are any abnormalities in chromosomes and translocations.

We have had 2 cycles, obtained 35 oocytes, 12 embryos. We did PGT-A, unfortunately, none were good. I have translocation balanced with 7 and 8. Anything you can advise?

With translocations, it’s very difficult to achieve normal embryos, it’s between 15 to 30% of possibilities to find good embryos, but of course, you had 12 embryos, so I would say before going ahead not only consider the translocation but perhaps also check if there are any problems with sperm DNA fragmentation. That could also increase the risk of abnormalities. With 12 embryos, it should be feasible to find a normal euploid embryo.

Does genetic testing increase pregnancy rates in older women?

That’s a very good question. Comparing one embryo without PGS with one embryo with PGS, talking specifically about women of advanced maternal age, should increase the pregnancy rate. In a 42-year-old woman, the risk of abnormalities is extremely high. If we only focus on normal embryos, then the percentage of implantation and ongoing pregnancy is much higher compared to no tested embryos. That’s the reason why with 1 tested euploid embryo, and with 1 non-tested embryo, the percentage is absolutely different. There is some evidence that suggests that older women who don’t have a very good ovarian reserve and a lot of embryos do not do the procedure. We know this is invasive and has some risks, so probably it won’t be recommended, but of course, again, we always prefer to work and focus on only euploid embryos.

I am 41, my AMH was 3.59 pmoles/ML in March 2020. I have done a few mild simulations, resulting in 2 frozen embryos. I would like to try a long protocol with the Diphereline on day 21 of this cycle. Some doctors recommend it, others say the long protocol isn’t good for low AMH. What is your view on this?

I wouldn’t recommend a long protocol with a low ovarian reserve because it takes a long time, and normally, in my experience, we don’t receive the same number of eggs, even less. I wouldn’t recommend it, I would just recommend a contraceptive pill if you haven’t used that, but not long protocol.

Can you explain how does DNA fragmentation work? I have translocation balanced with 7 and 8. My husband’s karyotype is okay.

You have the main risk of translocation in the karyotype of the eggs, but as I said, with the good number of embryos that you had (12), we should consider the sperm, we should check if the karyotype is all right and also if DNA fragmentation is good. It means that if internally, the head of the spermatozoa is damaged, it could also be a problem of this balancing chromosomes in the embryos. There is fragmentation testing, not only single but also double DNA fragmentation. Your partner’s sperm sample would be checked to see if, in the head of the spermatozoa, the DNA has interruptions, which would mean we need to improve this. Even though your husband’s karyotype is okay, I would strongly recommend studying the DNA fragmentation before the next round because, with all this number of embryos, it’s quite unlikely not to be able to find at least 1 euploid embryo.

Is PGT-A recommended in embryo adoption?

If PGT-A is not already done in embryo adoption, I wouldn’t recommend it. If the embryo is already frozen, it would be very invasive for the embryo to do the thawing and the biopsy. If you asked me if it is good to adopt PGT-A tested embryo, I’d say it’s very good, but it’s not necessary. In Spain, when it comes to embryo adoption you can only have access to embryos coming from women less than 35 years old, which means that the risk of problems with chromosomes is low, but it’s never 0%.

Would you recommend testing a frozen embryo for PGT-A? Or is it too risky to thaw it for testing?

I would never recommend doing PGT-A for frozen embryos because we have confirmed in our own data that even though the biopsy is successful, and the embryo reveals the normal chromosomes, the pregnancy rate is very low because it’s very invasive, so it’s not recommended.

Can you please explain the protocol you mentioned with the contraceptive pill? I was recommended mild stimulation with Gonal and Menopur?

Contraceptive pills should be taken a month before the previous period that you’re going to do the IVF. It will probably improve the synchronization of your follicles, which is the same objective as with the long protocol. That’s the reason why I would probably recommend it in your case. You should be taking it for 10 to 12 days, not longer. This also can be decreasing your response if you’re on the contraceptive pill for a long time.

Is there anything I could do to get my best genetic egg out?

Unfortunately, every single woman has her own egg quality. It’s not a 0%, so I would encourage you to go ahead with another round.

As I said, exclude other problems with the sperm, and if not, just reconsider different stimulation and try perhaps the next 2 rounds, and I believe you will be able to find a euploid embryo.

I went for an IVF procedure, and 23 matured eggs were retrieved. 14 were fertilized, but only 3 got to day-3, and none got to day-5. Is it a result of the genetic composition?

I don’t think so. I think it’s more to do with quality, so not chromosomes but quality. You should talk with your GP and try to see if you can do some melatonin protocol to try to reduce possible problems with your eggs and antioxidants, but you need to remember every woman has its quality, and there’s not a lot we can offer to improve quality.
Understanding the Importance of Carrier Genetic Testing
Hysteroscopy before IVF:  can it improve outcomes?
Recurrent Pregnancy Loss challenges: causes and solutions
How to prepare for an embryo transfer to improve your chances: There’s more to consider than just the endometrium
Endometrial factor and recurrent failures in IVF: diagnosis and treatment
How old is too old for my IVF treatment?
Laura Garcia de Miguel, MD

Laura Garcia de Miguel, MD

Dr Laura García de Miguel has worked in the field of gynaecology and obstetrics since 2008. At present, she is a medical director of Clínica Tambre in Madrid, Spain. Dr García de Miguel has extensive experience in IVF and provides a highly personalized approach to each and every patient and custom-tailored treatments to meet the needs of various patients. Dr García de Miguel specializes in treating patients who have had previous IVF failures or who respond poorly to hormonal or IVF treatment. Dr Laura speaks fluent Spanish, English, and French and treats patients from all over the world.
Event Moderator
Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.
Have questions about what factors will affect your IVF success?
Join our live event to directly ask your questions to three IVF experts.