In this live event, Dr Clara Colomé
, Medical Deputy Director at Eugin International, Barcelona, Spain, has talked about advanced maternal age and shared 4 various IVF cases that ended up with a successful outcome.
Advanced maternal age – factors
The mean age of women having their first child is increasing in Europe and all over the world. For example, in Ireland, Spain, Italy or Greece, the mean age for the first child is over 30 years old, in Spain it’s 32 after Italy. These trends can be observed all over the world. That’s why today, giving birth after 40 is twice more frequent than 20 years ago. When we take a look at all different countries all over the world, we can see e.g, in the US, in the 80s, the birth rate at 40 was around 5%, now it’s almost 15%. This is also a trend in Sweden, Russia, etc. This is due to social changes because women want to have a career, they are working more regularly than 50 years ago, and they want to establish personal and professional life before deciding to have a child. That would be okay if it wasn’t for nature because it hasn’t prepared us for that. Women have a determined number of eggs since birth, no more oocytes are produced during life. They are used until they’re over. Ovarian reserve usually starts decreasing faster after 35 years old, and this is related to the chances of natural conception.
At 20, the chances of having a child are very high, it’s over 80%, but when a woman reaches 40, it gets more and more difficult to conceive naturally, and on top of that, there is an additional higher risk of miscarriage. The higher risk of miscarriage is linked to oocyte quality and aneuploidy, which means chromosomal abnormalities. The older women get, the fewer oocytes she has, and those remaining in the ovaries have accumulated alterations because they’ve been there for over 40 years. That means the chances of having chromosomal abnormalities when the embryo starts multiplying increase.
When we analyze the miscarriage material in abortions following an IVF or an ICSI procedure, we see that the chances of the cause being an aneuploid embryo increases, especially after 40 years old. The chances of aneuploidies and chromosomal abnormality increase with age. This is something that we have to face more and more every day, and we have to find solutions for this kind of problem because currently, almost half of our patients are already 40 years old.
Dr Colomé presented a graphics with statistics from Eugin clinic, where 47% of patients currently undergoing treatment are 40 years old and older, usually between 40 and 44-45. There have been different population studies about the awareness of fertility and age and all these studies analyse the possession of patients of women who try to conceive after 40 showing there’s a lack of knowledge about fertility and age. The studies have shown that while many patients are aware that when they reach 40 years old, it might be harder to conceive, they think they will go to a fertility centre and have a baby. There’s an excess of confidence in ART (Assisted Reproductive Treatment), and although the technological advances in ART that have happened in the last 20 years have had little impact on the prognosis of patients 40 years old and older and yet pregnancy rates are not very high in this range of age, and there’s a high risk of pregnancy loss. The first mean age for the first IVF in Spain is already 38 years old, which is already advanced maternal age. 20% of the treatments in Europe are performed on women over 40.
Advanced maternal age – real-life cases
- 42-year-old woman, a homosexual couple, hypothyroidism treated with Levothyroxine, no previous pregnancy, BMI – 29
The patient had a slight thyroid problem which was correctly treated, she had removed the polyp through hysteroscopy, she had regular cycles, and she had never tried to conceive, she was slightly overweight, and her baseline hormonal test that we usually performed around the day 2 to 5 of natural cycles showed an elevated FSH, which is usually linked to a low ovarian reserve. This was also confirmed with a vaginal ultrasound, where the Antral Follicle Count (AFC) was around 5. She had also performed hysterosalpingography to check if her tubes were okay and if they were permeable. The couple decided to go for an IVF with their eggs and donor sperm to maximize pregnancy rates compared to artificial insemination. We went for a stimulation protocol with a high dosage of hormones and in an antagonist protocol which is what we typically use, and we obtained 4 oocytes which were fertilized after ICSI with donor sperm, and we managed to obtain 2 embryos that were transferred on day-3 of embryo development. The result was negative, but since this couple had never tried before, we went for a second round of IVF. We slightly changed the protocol, and we found during the second checkup that there was only 1 follicle developing this time, so we discussed with the patients and decided to balance the risk and the benefits. They decided to try an artificial insemination donor sperm, and as there was only 1 follicle developing, they wanted to avoid the anaesthesia and pick-up procedure, and that’s what we did. We triggered the ovulation, and then we injected sperm from a donor since her tubes were okay, we achieved the pregnancy, and they had a healthy baby boy 9 months later.
When we stimulate patients over 38 or over 40, there’s a chance of low response to an IVF stimulation. In this case, we try to always discuss with the patient the options. It’s always best to discuss the pros and cons:
- proceed with the oocyte pickup as planned plant assuming the risk of not having any embryos to transfer
- transform the cycle to artificial insemination (if tubes and sperm are okay)
- cancel the cycle and discuss oocyte donation
The next case presented a heterosexual couple, the woman was 43, and they had 4 years history of infertility. The patient had removed a fibroid a few years back, they had no previous pregnancy, she had long cycles, and the partner didn’t have any particular history, they hadn’t done any treatment.
- a 43-year-old, no previous treatment, 4 years of trying to conceive with a partner
We performed all hormonal tests that revealed an elevated FSH level, low AMH level at 0.1 ng/ml, and the AFC result was 2 follicles, which is very low. On the male side, the sperm was normal, so we discussed the options with the patients, usually, if the woman is 43 years old and older and has a low ovarian reserve, we have a tendency to at least offer the possibility of changing the female gamete and go for an oocyte donation, but this couple had never tried before, so they wanted to try with own eggs. Since we didn’t expect a very high response, we tried a modified natural cycle which is a very mild stimulation protocol, and we obtained 1 mature oocyte, but unfortunately, there was a fertilization failure. This happens when we only have 1 follicle. At that point, the couple decided to go for an egg donation.
In Spain, all donors are less than 35 years old, so they have good quality and quantity of ovarian reserve. We obtained 6 embryos, and we only transferred 1 on day-5, we transferred a very good blastocyst, and the patient is currently pregnant.
The 3rd case presented a woman at 41, they’ve tried to conceive naturally for 6 months without success. The woman had mild endometriosis and she had removed a cyst a few years back and had removed a fibroid from her uterus, no previous pregnancies, regular cycles, normal BMI, and a low ovarian reserve at 0.7 ng/ml. The vaginal ultrasound showed a correct number of follicles.
- a 41-year-old with a partner, no previous treatments, low ovarian reserve and endometriosis, partner’s semen analysis was normal
The male partner had no relevant medical history, no previous children and a normal sperm count. The couple wanted to try with their eggs, we did 1 IVF cycle with a higher dosage stimulation of an antagonist protocol. We obtained 2 oocytes, both fertilized, and the embryos managed to develop up until day-3. We transferred 2 day-3 embryos, but it didn’t work. Since we had managed to get to the end of the procedure, the couple tried again, but unfortunately, there was only 1 follicle developing, and they decided to cancel the cycle. We started a new cycle, we slightly changed the protocol and this time, we obtained 5 oocytes, 4 fertilized with the partner’s sperm through ICSI, and we transferred 2 embryos on day-3. They have a baby girl who is almost 1 year old now, and the couple has 1 frozen embryo from the same cycle.
We usually recommend doing a maximum of 3 or 4 IVF cycles because after that we see that pregnancy rates do not increase, it can work, but cumulative pregnancy rates start to decrease up until 3.
The fourth case presented a heterosexual couple. A 44-year-old woman, this couple already had children together, they had 2 previous children that were aged 7 and 5 after 2 IVFs that had been performed at 37-38 years old. They had a history of IVF that had worked a few years back, but she was 37-38. She had a regular cycle partner and had no relevant medical history. They had already performed an IVF cycle in another centre with a negative result after transferring 2 day-3 embryos.
- a 44-year-old, 2 previous successful IVF cycles in the past, recent IVF failure
We did hormonal tests that showed normal FSH, and an AMH that was quite good considering the age, it was 1.7 ng/ml. She had some follicles on her ovaries, and the sperm was normal. Due to age and the previous failed IVF cycle, we advised them to go for egg donation, but they were not ready for that, they had already had children through IVF, so they wanted to try again. We went for an IVF with a higher dosage stimulation protocol, we obtained 5 oocytes, 4 were fertilized which is a very good result, and we transferred 2 embryos on day-3, and they implanted, there was a positive pregnancy test, there was the first ultrasound with a positive heartbeat, but unfortunately it was a miscarriage at 8 weeks of pregnancy. At this point, we didn’t have any embryos left embryos, so the patient accepted that even though she managed to get pregnant with her own eggs, there was also a risk of miscarriage or chromosomal abnormalities. Therefore, they decided to accept egg donation, we inseminated the oocytes from the donor with partner frozen sperm through ICSI, and we obtained 7 embryos, we took them to day-5, blastocyst stage, and we transferred 1 blastocyst but unfortunately, it was negative. We had 6 frozen blastocysts, so we decided to do a natural preparation cycle for the endometrium where we monitored the natural ovulation cycle, and we transferred another blastocyst that was thawed on the same day to this patient’s uterus, and she’s currently pregnant with another baby girl.
When we discuss all the options with patients of advanced maternal age, we always have to inform them about the risks associated with pregnancies over 40 years old. Those are mostly miscarriages, and aneuploidies, but also obstetrical pathologies, such as diabetes, preeclampsia or pre-term labour. Some of these risks are minimized with the use of donor oocytes. However, other risks such as diabetes or preeclampsia, which is high blood pressure during pregnancy, are linked to age, especially to the patient’s health status. That’s why we also monitor the weight, we advise the patients to quit smoking, we always need to control the thyroid function, we need to make sure before conceiving that other risk factors are as minimal as possible to achieve a healthy child which is our goal.