Age is the strongest determinant of treatment success in women seeking fertility advice. Although pregnancy rates after spontaneous conception or ART are relatively good up to 36-37, live birth rates significantly decreases with age. The decline in fertility associated with a higher oocyte and embryo aneuploidy in women of advanced age is deeper in the age of over 40, given that in these patients the miscarriage rates exceeds 30%.
To overcome the gap associated with age-related fertility loss, below we will discuss treatment options available for women of advanced age.
Age Related Fertility Loss
The number of oocytes decreases naturally and gradually, although due to the process of atresia. Fecundity of women gradually decreases with age, with a sharp, significant decrease observed at the age of 37. This age-related fertility decline is also accompanied by a significant increase in the frequency of aneuploidy and spontaneous abortion.
Accordingly, a decrease in oocyte yield and oocyte quality (i.e. “ovarian aging”) are the main reasons for the deterioration of IVF results with the age of females, with the quality of oocytes that determines most of the quality of the embryos, and the quality of the embryo that determines most of the pregnancy and live birth rates. Undoubtedly, age is the best predictor of live birth rates and a key component in understanding the female reproduction.
Intrauterine Insemination (IUI) or In Vitro Fertilization?
Infertile counseling is one of the most unpredictable and beautiful parts of everyday clinical practice, as it is full of dilemmas. The decision whether to directly offer patients IUI or IVF for the most effective treatment of their fertility problems is a complex decision that must take into account a variety of factors, including not only the success rates of each treatment, but also the various factors affecting fertility, and obviously, female age.
IUI is often the first choice for most couples in which the number of motile spermatozoa is reasonable, and tubal patency is confirmed. The age of women should always be taken into account, given that the available data indicate disappointing pregnancy rates after IUI in women of advanced age, for whom the conception time is critical.
On the other hand, the level of fertility after IVF is 8-10% for the initial cycle in women older than 40. The results showed a significant decrease in live birth rates for each additional year in age.
Consequently, the accelerated decline in the ovarian reserve of women of advanced age and the high incidence of embryo aneuploidy that occurs in women older than 40, IVF as a first-line treatment may be the best option for this group of infertile patients.
Ovarian Stimulation in Women of Advanced Age
The proportion of women aged 40 or over attending IVF/ICSI is at least 25% of all cycles in Europe. Methods of ovarian stimulation in women of advanced age were obtained from studies in poor ovarian responders and young women with unexplained infertility.
On the other hand, the conclusion about inexplicable infertility, obtained in young women to the age-related infertility of women of advanced age, is inappropriate.
Natural IVF Cycle and Oocyte Accumulation
The natural IVF cycle showed very good pregnancy rates in the general infertile population with a cumulative pregnancy probability of up to 46%, and this mild approach can be an alternative realistic treatment for many women wishing to avoid ovarian stimulation. Nevertheless, poor respondents are disappointed with the low live birth rates, which does not exceed 3% per cycle, regardless of the age of the patients. In this regard, there is insufficient evidence to recommend IVF as an alternative treatment in women with poor prognosis.
On the other hand, the idea of oocyte accumulation is based on the assumption that an increase in the number of retrieved oocytes will allow poor respondents to hope for the status of a norm-respondent and will give similar results. Vitrification, as an excellent method of cryopreservation, can serve for this purpose by creating a large stock of oocytes accumulated after several cycles of stimulation and inseminated at the same time in the future, in an attempt to create more embryos available for embryo transfer.
Preimplantation Genetic Screening (PGS)
The goal of PGS is the transfer of euploid embryo aimed at achieving a healthy pregnancy. Although the universal application of this technology to all infertile patients undergoing IVF is the subject of discussion mainly because of its cost, it seems that women of advanced age can take advantage of PGS.
However, even if the clinical pregnancy and live birth rates seem to be higher in older patients undergoing PGS using advanced methods of 24-chromosomes screening, it seems that this advantage is only for those who reach the stage of embryo transfer, and have euploid embryos to transfer, since the advantage per cycle in this age group is not persist. Thus, the use of PGS appears to be important only for a small subset of patients with poor prognosis that respond well and produce good quality embryos.
Women of advanced age should be advised that in order to achieve a single euploid embryo transfer, they might require several IVF cycles.
Initially, oocyte donation was developed as a therapy for young women with premature ovarian failure, and not as a means of overcoming the age-related decline in fertility. However, age-related infertility is one of the most common causes of the use of oocyte donation, especially in women older than 40. It was reported that the total pregnancy rates after 4 cycles of embryo transfer are up to 90% regardless of the age of the recipient.
However, obstetric and neonatal complications associated with advanced maternal age should not be overlooked, especially given the growing demand for oocyte donor availability. A recent analysis showed increased risks of hypertensive pregnancy disorders, pre-eclampsia, low birth weight, preterm delivery, caesarean delivery and postpartum hemorrhage in pregnancy after oocyte donation versus IVF or spontaneously conceived pregnancies.
Finally, differences in donation programs exist in different countries and raise ethical and legal issues, such as donor financial compensation, their anonymity and waiting time for registered patients in the donation program.