ART techniques for women of advanced maternal age (+38)

Dr Elias Tsakos, Fertility Expert and Medical Director of Embryoclinic, discussed and explained the latest advancements in Assisted Reproductive Technology tailored to women over 38.

Defining Advanced Reproductive Age

In most scientific textbooks and journals, we find that 35 years and older is the beginning of the definition of advanced reproductive age. However, the average age of female patients seeking fertility treatments is just under 39 (38.8 years). So, we know that after the age of 35, the chances of conception decrease, affecting both natural fertility and assisted reproductive techniques. Additionally, there is an associated risk of adverse outcomes.

Why is advanced maternal age an issue? One crucial aspect is genetic anomalies, with the chance of genetic anomalies leading to either failure, miscarriage, or abnormality being more likely as fertility diminishes. This affects not only the quantity but also the quality of eggs. There is also an increased maternal risk due to factors associated with age, including uterine pathology, infections, cervical anomalies, and general medical conditions like diabetes, hypertension, and obesity.

As for the ovaries, there is a reduced ovarian reserve, with the quality and function of eggs diminishing with advanced age. This decline begins in the late 20s, accelerates around the age of 35, and decreases further after the age of 40, nearly disappearing after 45.

It’s essential to understand that the reduction in fertility applies to natural and assisted fertility, and IVF success rates primarily depend on the female’s age. There is also an increased risk of miscarriage in this age group, which may be due to a combination of factors.

General health concerns are significant, especially in preconception care, where we need to assess and counsel women wishing to become pregnant. These concerns include a higher chance of malignancy, cardiovascular risks, metabolic syndrome risks, and thrombotic risk, which can be associated with factors like hormonal stimulation and pregnancy. Screening for cervical pathology and HPV testing is also crucial.

In summary, just as you wouldn’t start a journey across Europe in your car without a comprehensive service, it’s unwise to embark on a fertility journey without a thorough assessment of all potential risk factors. These factors can affect not only the success or failure of IVF but also the success or failure of pregnancy and a woman’s general health and well-being. This applies to uterine dysfunction, fibroids, adenomyosis, endometriosis, and uterine polyps. The uterus must be in perfect condition, not only for successful fertility but also for the woman’s health, as we occasionally diagnose cases of uterine cancer, which underscores its importance.

The impact of age on female fertility

The more advanced the female’s age, the more likely it is that we may find something important. Equally, it may be important for success. There are conflicting reports in the literature. In 2023, the majority of women undergo IVF without a formal assessment of the uterine cavity or the fallopian tubes. Not all fibroids need removal, however, the uterine cavity, at least the endometrium, has to be evaluated. Even when there’s no suspicion from the scan, roughly 20% of small polyps are not visible on scans, even in the best hands. They need to be addressed, treated, and sorted out with a biopsy before proceeding.

Obstetric teams are improving, but all pregnancy complications are much higher with advanced maternal age.

I can’t stress enough the value and importance of single embryo transfer, especially after the age of 40, where the chances of complications increase.

Primary fertility treatment options

The journey begins with fertility treatment and pre-IVF testing. It’s essential to assess and optimize before embarking on the treatment. There’s a wide range of options, including IVF, ICSI, embryo donation, and even gestational surrogacy in specific cases. Genetic testing is also crucial in the assessment. Pre-IVF testing is vital. It includes basic testing and more advanced tests. Microbiome assessment may be necessary, especially in cases of repeated unexplained failures. Genetic testing is essential, but the depth of testing varies depending on the complexity of the case.

Pre-IVF testing starts with basic assessments and progresses as the case becomes more complex. In some cases, endometrial platelet-rich plasma (PRP) may be beneficial, particularly for women with advanced reproductive age, implantation failures, miscarriages, or adhesions. Sperm quality should not be overlooked. The assessment of male infertility is a growing field, and it’s essential to explore sperm quality comprehensively.

Treatment options

There is an egg donation option, embryo donation but also surrogacy. Surrogacy is usually the last resort. If you’ve tried everything, or there are factors like malignancy, Rokitansky syndrome, multiple fibroids, or hysterectomy, there’s no chance of carrying your own baby. There is also a new method like uterus transplantation which is also gaining recognition. More reports are emerging from around the world, and it seems that Europe, especially the Swedish team, leads in this field. Uterus transplantation may become a more viable option for patients worldwide in the next 3 to 5 years, before or alongside surrogacy.

Supplementary options include pre-genetic testing, PRP for rejuvenation, hysteroscopy, and robotic surgery. The efficacy of PRP is still being explored, especially in identifying which subgroups of patients might benefit. Hysteroscopy seems helpful, especially for women of advanced reproductive age. Robotic surgery, which has been around for over 20 years, is here to stay. There is less chance of conversion to laparotomy, reduced blood loss, and improved outcomes.

Conclusions

In conclusion, advanced reproductive age is becoming more common in assisted reproduction. Women of advanced age face poorer fertility outcomes and a higher risk of adverse events. Therefore, it’s crucial to provide comprehensive counseling and pre-fertility testing. There are multiple options available, and the choice depends on individual indications. Additionally, there are various supplementary methods to improve outcomes.