During this event, Dr Elena Santiago, Gynaecologist & Fertility Specialist at Vida Fertility Institute, discussed options for women struggling with fertility in their 40s.
For many women, trying to conceive after the age of 40 can feel overwhelming, especially when previous attempts have not been successful. In this session, Dr Elena Santiago, Gynaecologist and Fertility Specialist at Vida Fertility Institute in Spain, explained why fertility declines with age and outlined the treatment options that may still be available for women over 40 pursuing IVF.
Dr Santiago emphasised throughout the presentation that there is no single solution for everyone. Each case must be individualised, based on ovarian reserve, egg quality, medical history, and personal circumstances.
Dr Santiago explained that the main reason fertility becomes more challenging after 40 is age-related changes in both the quantity and quality of eggs. Women are born with a finite number of eggs, and this number decreases steadily over time. As ovarian reserve declines, the chances of retrieving eggs during IVF stimulation are reduced.
Egg quality is an equally important factor. Even when ovarian reserve appears relatively preserved, egg quality tends to decline with age. This leads to a higher proportion of embryos with chromosomal abnormalities. Dr Santiago noted that these embryos may fail to implant or may result in miscarriage, particularly during the first trimester.
She explained that this is the main reason pregnancy rates decrease and miscarriage rates increase as women get older.
Dr Santiago described two key tools used to evaluate ovarian reserve. The first is a transvaginal ultrasound to count antral follicles in the ovaries. When the total number of antral follicles is between 10 and 20, ovarian reserve is generally considered normal. Fewer than 10 follicles usually indicates a low ovarian reserve.
The second assessment is a blood test measuring anti-Müllerian hormone (AMH). AMH levels help estimate how many eggs remain in the ovaries. These two tests together provide a clearer picture of a woman’s fertility potential.
However, Dr Santiago stressed that ovarian reserve alone does not determine success. Egg quality remains a limiting factor, particularly after the age of 40.
Age does not only affect the ovaries. Dr Santiago explained that other conditions become more common with time and can also reduce fertility. These include endometriosis, fibroids, uterine polyps, and general medical conditions such as hypertension or diabetes, all of which may affect conception or pregnancy progression.
Male factors should also be considered. Although men continue producing sperm throughout life, age can affect sperm quality. Dr Santiago highlighted increased oxidative stress and higher DNA fragmentation in sperm as men age. This may influence fertilisation, embryo development, and implantation.
DNA fragmentation testing can help identify whether additional interventions are needed, such as antioxidant treatment, sperm selection techniques, or genetic testing of embryos.
Dr Santiago outlined several treatment strategies that may be considered for women over 40, depending on individual circumstances.
One option discussed was ovarian rejuvenation using the patient’s own platelet-rich plasma. Growth factors derived from the patient’s blood are injected directly into the ovaries during a procedure similar to egg retrieval.
This treatment is typically offered to women under 45 with low ovarian reserve and is performed in the cycle before ovarian stimulation. The goal is to increase AMH levels and antral follicle count to improve response during IVF.
Dr Santiago described this approach as experimental, noting that while results can be encouraging in some patients, it does not work for everyone, and more evidence is still needed.
Preimplantation genetic testing for aneuploidy (PGT-A) was presented as an important tool for women over 38. This involves biopsying good-quality blastocysts on day five or six and analysing their chromosomes.
Dr Santiago explained that PGT-A helps identify chromosomally normal embryos with a reliability of around 90%. Transferring euploid embryos increases the likelihood of implantation and reduces the risk of miscarriage.
Another strategy Dr Santiago discussed is dual stimulation, or DuoStim. This approach involves performing two ovarian stimulations within the same menstrual cycle: one in the follicular phase and a second in the luteal phase.
She explained that the ovaries recruit follicles in multiple waves throughout the cycle, not only at menstruation. By stimulating twice, clinics may collect more eggs in a shorter time frame, increasing the total number of embryos available for testing or transfer.
Dr Santiago noted that dual stimulation is generally well tolerated and may reduce costs compared with two separate cycles. Studies have shown similar embryo quality and chromosomal status between embryos obtained in the follicular and luteal phases.
Despite advances in IVF, Dr Santiago emphasised that egg donation remains the treatment with the highest success rates for women with very low ovarian reserve, poor egg quality, or repeated IVF failures.
She explained that in Spain, egg donation is anonymous and strictly regulated. Donors are carefully selected, medically and psychologically screened, tested for infectious and genetic diseases, and matched to recipients based on physical characteristics. Genetic compatibility testing can also be performed when required.
Egg donation is often recommended for women over 45 or when multiple IVF cycles with own eggs have not been successful.
Dr Santiago outlined the typical egg donation process. Fertilisation can be performed using fresh or frozen sperm, and embryos are cultured to the blastocyst stage. Most clinics prefer frozen embryo transfer for logistical reasons, although fresh transfer may be considered in some cases.
Endometrial preparation can be done using hormone replacement or, in selected women with regular cycles, a natural cycle approach.
In her conclusion, Dr Santiago highlighted several key points. Fertility outcomes are strongly age-dependent, and earlier intervention generally leads to better results. For women over 38, adding genetic testing can improve IVF success. When ovarian reserve is very low, strategies such as PRP or dual stimulation may help increase egg numbers.
When these approaches are unsuccessful, egg donation offers the highest chance of achieving pregnancy. Dr Santiago stressed the importance of personalised treatment planning and informed decision-making.
She encouraged women to seek expert guidance early and to understand all available options in order to choose the most appropriate path toward achieving pregnancy.
Yes, we do offer embryo adoption. Currently, we have embryos at the blastocyst stage, but it’s true that while it’s always a possibility, the pregnancy rates are generally a bit lower than with egg donation treatments.
The embryos are the ones left over from patients who have achieved pregnancy and no longer wish to try again. These embryos are then given for donation. One of the requirements is that women must be under 35 years old when they do the treatment and achieve the embryos. This is the same as with egg donation. However, sometimes the embryos may have lower quality, although the pregnancy rates we can offer are still around 50%. Additionally, the tests done on these embryos may not be as extensive as those done for egg donors, which is another reason the pregnancy rates may be a bit lower.
Mini IVF does make sense, but as with any treatment, we always need to individualize the approach. It may not be the first option we normally use for ovarian stimulation. However, if we have already tried a maximum dose with other medications, and it hasn’t worked well, we may try mini IVF for a second or third round, understanding that this means mild stimulation. Adding Clomid is a good option, especially if we’re not doing a fresh embryo transfer.
The cost depends on the options we consider for each patient. The lowest price would be around €4,000. The highest price, if we are using PRP, PGT-A testing, or the time-lapse incubator, could go up to around €8,000. For egg donation treatments, it’s similar, with the maximum price being around €10,000 when using PGT-A testing. For more details, it’s always best to directly contact the clinic. I can show you the contact information after we finish the questions.
It depends on the baseline situation of each patient. Normally, if the ovarian reserve is good or high, meaning there are no risks of hyperstimulation, we do not offer the possibility of dual stimulation, as the goal is to achieve a large number of embryos. This treatment is typically necessary for patients with low ovarian reserve, where there is no risk of hyperstimulation syndrome.
Unfortunately, due to age, I don’t think PRP would work in this case. Sometimes, for younger patients with premature ovarian failure, we can try PRP because the quality of the eggs is a bit better. However, from 45 years onwards, I believe the best option would be to consider egg donation directly.
At least you’ve tried, and now we know. I believe the next step is egg donation. I know it’s not easy, but many patients achieve their babies with egg donation treatments. Making the decision is the hardest part; once you do, everything becomes easier.
We recommend antioxidants such as DHA and zinc, which are commonly found in fertility supplements for men. Additionally, it’s important to add treatment with calamine, as we’ve seen it helps a lot in lowering DNA fragmentation. It’s also essential to be consistent with the treatment; it usually takes at least three months to see a good change, since the sperm cycle lasts that long. Furthermore, lifestyle habits play a crucial role. For example, if a man is a smoker and continues smoking while undergoing antioxidant treatment, we may not see significant changes. It’s a combination of antioxidants and healthy lifestyle habits.
It depends on the type of DNA fragmentation, whether it’s double-strand or single-strand. For double-strand fragmentation, we normally use techniques such as Zymote, also known as Fertile Chip. For single-strand fragmentation, we use a technique called SpermSlow.
However, the choice of technique also depends on the sperm collection quality on the day, as density, motility, and concentration can affect what techniques are possible. If the sperm selection technique isn’t applicable, we can use the alternative technique. For donor eggs, these eggs typically have better quality and can repair some DNA fragmentation, but not always. If DNA fragmentation is high, we would still need to use sperm selection techniques to get the best results with egg donation.
Donor eggs, especially from donor eggs, due to their better quality, can repair some DNA damage. However, they don’t always fully repair it. In some cases, we may still see low fertilization rates or poor-quality blastocysts even with normal sperm count, and upon testing DNA fragmentation, we find it to be high. This shows that even with egg donation, we may need to use sperm selection techniques to improve the outcome.
Normally, we follow global parameters, with the ideal sperm concentration being around 32 million sperm in a sample. However, it also depends on the volume of the sample, the day it was collected, and other factors.
Current evidence does not prove that EmbryoGlue is more effective for embryo transfer. In our opinion, we do not use EmbryoGlue in our lab because we are not certain that it significantly helps with implantation.
After several unsuccessful embryo transfers with double donation, it’s important to evaluate other factors, including the immune system. Endometriosis can cause inflammation, which can affect implantation. Steroid treatments can help reduce this inflammation and make the endometrium more receptive. However, this treatment should be managed by a specialist, typically an immunologist. It’s also crucial to check for other factors, such as the uterus’s morphology, the endometrium’s condition, and the window of implantation. Combining immune treatments with this evaluation can be a good approach.
