In this webinar, Dr Oliver Pack, Fertility Specialist discussed all the latest advances in reproductive medicine in 2023. Dr Pack talked about PGT-A, advanced maternal age, egg donation, fertility preservation, and ovarian reservation. He has covered the techniques applied in treatments and some ongoing investigations into experimental treatments.
Starting with a brief overview of Reproductive Medicine and fertility treatments in Spain. Based on data from 2020, Spain ranks as the third country with the highest number of fertility treatments. India and Turkey hold the first and second positions, respectively. One of the primary reasons Spain is relatively advanced in this field is due to the significant volume of people who come here for treatment, particularly for egg donation. Spain is a popular destination for egg donation treatments, attracting patients from around the world due to its high success rates.
Currently, around 9% of pregnancies are achieved through ART. Couples typically undergo IVF due to male-factor infertility, female-factor infertility, or a combination of both. Male factor infertility can often be resolved through techniques such as intracytoplasmic sperm injection (ICSI), which has been in use for many years and is highly efficient in addressing sperm-related issues.
On the other hand, resolving female factor infertility is more challenging as it depends on various causes. It is not uncommon for multiple factors to contribute to the inability to conceive, including issues with fertilization, implantation, and early-stage embryo development during the first trimester. Pinpointing a single cause can be difficult, and even if implantation fails, identifying all contributing factors can be a complex task.
Approximately 30% of infertility cases have a mixed origin involving both male and female factors. Furthermore, 40% of treatments are related to advanced maternal age, which is a significant concern. The age of the female partner plays a crucial role in fertility, as women produce eggs that are the same age as they are. This leads to challenges in both egg quality and quantity, as the ovarian reserve diminishes over time, and eggs cannot be regenerated. The number of viable eggs decreases each month, with only one dominant follicle growing and potentially being fertilized. Advanced age in women, typically considered to be over 40, significantly impacts the chances of success. The window of opportunity to achieve pregnancy becomes narrower as women approach their late 30s and early 40s, and beyond the age of 45, the chances of natural conception become nearly impossible.
Considering these factors, it is essential to focus on the age of the eggs rather than the age of the woman. Egg donation is a viable solution for women over 40 and even up to the age of 50, as it resolves the issue of diminished egg quality and quantity. However, for women who are 38 or younger, there are still chances of success with their eggs, although the quality of the embryos may be a concern.
Preimplantation Genetic Testing for Aneuploidy (PGT-A) can help identify embryos with missing or additional chromosomes, providing insight into their potential to develop into a healthy babies. However, it’s important to note that PGT-A does not determine the overall health of the future child; it focuses solely on chromosomal abnormalities. The detection of abnormal embryos allows for their exclusion from the transfer process, reducing the risk of unsuccessful implantation or the birth of a baby with certain chromosomal disorders.
In cases where blastocysts (embryos at the stage of development on day five) cannot be obtained, couples often seek egg donation as a solution. Statistics show that couples who pursue egg donation in Spain have typically undergone five failed IVF cycles before seeking this option. The reasons for IVF failures can vary, ranging from a lack of viable embryos to cancelled procedures due to inadequate follicle growth. Each step in the IVF process presents uncertainties, from follicle response to egg quality, fertilization, embryo development, and successful implantation. The goal is to reach the blastocyst stage, as embryos at this stage have a higher chance of successful development. However, even if a blastocyst is achieved, there is still a significant question of chromosomal health, which can be addressed through PGT-A.
In summary, while there is still a chance of success with IVF for women over 38, the probability decreases as age advances. Embryos obtained from older women are more likely to have chromosomal abnormalities, impacting their ability to develop into healthy babies. For couples pursuing IVF with such embryos, the success rates remain relatively high if a euploid (chromosomally normal) embryo is transferred. However, even in these cases, success rates do not exceed 60% for live births.
The success rate for assisted reproductive technologies (ART) is around 60%, which is not bad considering the viewpoint of embryos. However, the problem lies in women older than 42, where it becomes challenging to find a euploid embryo. Even if one is obtained, there might only be one. In such cases, we consider egg donation.
Egg Donation: For couples facing these challenges, egg donation is a viable solution. Spain, known as one of the meccas for egg donation, offers numerous donors who provide high-quality eggs. This allows for the production of many high-quality blastocysts with a high rate of successful implantation and live births, ranging from 45-50%. The advantage of using donor eggs is that if one cycle fails, another attempt can easily be made. Egg donation provides a nearly 100% solution for age-related issues such as low egg reserve and poor egg quality.
Ovarian Rejuvenation: In cases where egg donation is not an option or is not accepted by couples for personal or religious reasons, ovarian rejuvenation is an experimental treatment that can be considered. This treatment involves injecting platelet-rich plasma (PRP) into the ovaries to stimulate follicle growth and possibly achieve a higher number of eggs. However, the effectiveness of ovarian rejuvenation varies, and it strongly depends on factors such as egg reserve, quality, and age. Clinical trials are currently underway to determine its true efficacy.
Fertility Preservation: Fertility preservation, specifically freezing eggs, is highly recommended for women. Ideally, it should be done before the age of 37 when the egg reserve starts to decline rapidly (although it starts to decline at 35). Freezing eggs later than 37 presents challenges due to lower egg quantity and quality. Additionally, it’s important to consider that around 30% of frozen eggs may be lost during the thawing process. To ensure a good chance of success in the future, it is advisable to have at least 15 frozen eggs when a woman is under 37.
New family models: In recent years, there has been an increase in new family models, such as single women choosing to become mothers and same-sex couples. For single women, embryo donation or egg donation is often the best treatment option, especially if they are over 40. In same-sex couples, the reciprocal IVF method (ROPA) is commonly used, where one partner undergoes ovarian stimulation to retrieve her eggs, which are then fertilized with donor sperm. The other partner receives the embryo and carries the pregnancy.
Customized stimulation protocols have become a significant advancement in reproductive medicine. These protocols take into account factors like follicle count and AMH level, which are strongly related to age. The timing and type of stimulation are individualized decisions, and there is no general protocol that applies to everyone. Technological advances, including time-lapse imaging of embryo development, artificial intelligence for embryo grading, and advanced diagnostic tests, have improved the success rates of ART.
Treating Male Factor Infertility: Male factor infertility is a common issue, and various techniques can be used to address it. In cases where sperm quality is affected, methods such as magnetic cell sorting, sperm selection based on fragmentation rates and apoptosis, and advanced spermogram analysis can be employed to separate and select good-quality sperm.
In conclusion, the field of reproductive medicine has made significant advancements, offering solutions such as egg donation, ovarian rejuvenation (still experimental), and fertility preservation. New family models, including single women and same-sex couples, can benefit from these treatments. Customized stimulation protocols, advanced diagnostic tests, and techniques for treating.
Endometrial receptivity tests are genetic tests that analyze the cells of the uterine lining to determine the degree of receptivity. Biopsies are routinely performed, especially when the first embryo transfer has failed. The test provides valuable information about the optimal timing for embryo transfer, which is typically five days after starting progesterone. However, receptivity can vary, following a curve of increasing receptivity, reaching a peak, and then decreasing. By assessing receptivity, we can adjust the timing of progesterone in the natural cycle, increasing the chances of a successful transfer.
In addition to endometrial receptivity tests, we also conduct immunological testing, specifically for natural killer cells (KIR) and lymphocytes. We examine different cell types involved in the immune response against the embryo. Additionally, we perform HLA-C genotyping, which analyzes the compatibility between the receptors on natural killer cells and antigens on the embryo’s surface. Certain combinations of HLA-C types may not be compatible, potentially impacting pregnancy success rates. While these findings are not yet proven, they offer insights into potential factors affecting fertility.
Artificial intelligence is making its way into reproductive medicine as well. AI technology is being used to analyze embryo development and structure, assisting embryologists in embryo selection. By assessing images of embryos, AI systems can contribute to the identification of high-quality embryos, complementing the expertise of embryologists. Although AI’s role is currently limited to embryo selection, there is potential for future applications, including sperm selection. As AI continues to advance, it may become an even more valuable tool in reproductive medicine.
These advancements in reproductive medicine demonstrate the integration of technology to improve success rates and enhance patient outcomes. From endometrial receptivity testing to immunological analysis and the use of AI, these techniques offer a comprehensive approach to addressing infertility issues. While AI is still in its early stages in this field, its potential impact is promising. With ongoing research and development, we can expect further innovations that will continue to revolutionize reproductive medicine.- Questions and Answers