During this event, Dr Elena Santiago, Gynaecologist & Fertility Specialist at Clinica Tambre, Madrid, explained the implantation window, how to improve it and prepare the endometrium for the embryo transfer to achieve a positive outcome.
It is essential to understand the implantation window in order to comprehend fertility treatments and general fertility. During the session, Dr Santiago covered women’s physiology, the menstrual cycle, the role of the endometrium, the window of implantation, endometrial receptivity tests, endometrial preparation for embryo transfer, the implantation process, and recommendations to take home.
Women’s Physiology & age
To begin, let’s discuss women’s physiology and how the ovarian cycle works. Women are born with all their eggs (EX) in their ovaries, typically around 2 million. Unlike men who produce new sperm every three months, women do not generate new eggs throughout their lives. It is crucial to grasp this distinction. Additionally, contrary to the belief that only one egg is lost each month, women actually lose a substantial number of eggs during each menstrual cycle, with approximately 11,000 eggs dying each month until menopause. This loss occurs even in childhood before experiencing the menstrual cycle.
During puberty, which usually occurs between the ages of 10 and 16, significant changes take place in a woman’s life, including the reactivation of the gonadotropin-releasing system in the brain. This activation triggers the ovaries, initiating the menstrual cycle and maturation of the reproductive system. Bone growth and the development of secondary sexual characteristics also occur during this stage, culminating in menarche, the onset of menstruation. By the time of menarche, women typically have around 300,000 to 400,000 eggs remaining.
Throughout a woman’s reproductive years, she continues to lose eggs, with approximately 1,000 eggs lost during each menstrual cycle, regardless of contraceptive use, pregnancy, or nutritional supplements. It is worth noting that lifestyle factors can affect the quality of eggs and ovarian reserve. Contrary to common belief, fertility treatments such as IVF or ovarian stimulation do not deplete eggs or impact ovarian reserve. A woman runs out of ovarian reserve when her ovaries stop producing hormones, leading to the onset of menopause, which is confirmed after a year without menstruation.
The menstrual cycle
The menstrual cycle begins with the release of gonadotropin hormones (FSH and LH) in the brain, which stimulate the ovaries. As a result of this stimulation and follicle growth, the ovaries produce estrogen, followed by progesterone after ovulation. Oestrogens play a crucial role in thickening the endometrium, while progesterone prepares the endometrium for pregnancy. The endometrium is the inner lining of the uterus and undergoes changes throughout the menstrual cycle. If pregnancy does not occur, the endometrium is shed during menstruation.
During the follicular phase of the cycle, estrogen levels increase, leading to the growth of the endometrial lining. After ovulation, during the luteal or secretory phase, the endometrium becomes more receptive, facilitated by progesterone. This receptivity allows for implantation to occur. If implantation does not happen, the endometrium renews itself, resulting in menstruation. The interplay of ovarian hormones and the endometrium is vital for successful implantation and early embryo development.
The term “window of implantation” refers to the limited timeframe when the endometrium is receptive to implantation. Recent studies suggest that each woman has her own personalized window of implantation due to variations in uterine receptivity. Approximately 10% to 30% of infertility patients may have a displaced window of implantation. Understanding this concept is crucial in fertility treatments like IVF because the timing of embryo transfer aligns with the receptive window. Implantation failure may occur if the window of implantation differs from expectations.
The fertile window, when the endometrium is receptive, typically occurs around six to ten days after ovulation. However, this timeframe can vary among women depending on their menstrual cycle length. Women with cycles ranging from 25 to 35 days are considered to have ovulatory cycles, but the specific timing of the window of implantation differs. Tracking ovulation symptoms such as abdominal pain, changes in vaginal discharge, breast sensitivity, and changes in smell, or temperature can help identify the fertile window. Ovulation tests, which detect hormone levels in urine, are another useful tool.
In fertility treatments, assessing the window of implantation or endometrial receptivity is essential. Endometrial biopsy is a common method to analyze gene expression in the endometrium. This biopsy can determine if a woman is pre-receptive, receptive, or post-receptive. The results of these tests provide valuable information for personalizing embryo transfer protocols and improving pregnancy rates. These tests are typically recommended for patients with unsuccessful embryo transfers or unsuccessful transfers of genetically normal embryos (euploid embryos) after multiple attempts.
In conclusion, understanding the implantation window, the role of the endometrium, and endometrial receptivity is crucial in fertility treatments. Women’s physiology, the menstrual cycle, and the interplay between hormones and the endometrium play significant roles. Tracking ovulation symptoms and utilizing tests like endometrial biopsy can provide valuable insights for personalized embryo transfers. These approaches help optimize the chances of successful implantation and pregnancy.
The role of endometrium
The endometrium changes every month. Estrogen thickens the lining in the first part of the cycle, while progesterone prepares it for pregnancy. The endometrium survives and nourishes the early embryo by stimulating gland growth. The term “window of implantation” refers to the few days when the endometrium is receptive for implantation. Recent studies show that every woman has her personal window of implantation, which may be altered in infertility patients.
Calculating the window of implantation is important in IVF treatments to ensure the uterus is ready for embryo transfer. Implantation failure may occur if the window differs from expectations. Generally, the window of implantation occurs after ovulation, within the secretory or luteal phase, lasting around 6 to 10 days.
The length of the menstrual cycle varies among women, and the window of implantation depends on when ovulation occurs. Cycles can range from 25 to 35 days, with ovulation usually occurring within this range. Identifying symptoms of ovulation can help determine the window of implantation. Symptoms may include nausea, abdominal pain, spotting, transparent vaginal discharge, changes in smell, breast sensitivity, and temperature changes. Ovulation tests can also assist in identifying the fertile window.
Regarding fertility treatments, testing the receptivity of the endometrium is crucial. Endometrial biopsy is a simple procedure that analyzes around 300 genes, determining if the endometrium is pre-receptive, receptive, or post-receptive. This personalized information guides embryo transfer at the optimal time for implantation.
Endometrial Receptivity Testing
Endometrial receptivity tests are indicated for patients who have had multiple unsuccessful high-quality embryo transfers or unsuccessful euploid embryo transfers. If a healthy chromosomic embryo transfer fails, testing is recommended. Overall, it’s advisable for any patient seeking a better approach before undergoing an embryo transfer to consider these tests.
There are patients who have undergone multiple treatments, such as egg donation and are about to undergo their first embryo transfer. They want to know if their window of implantation is normal or if there are any differences. Additionally, some patients may only have one high-quality embryo for transfer and would like to undergo testing before proceeding to minimize the risk.
It’s important to note that endometrial testing is typically done in preparation for frozen embryo transfers. This involves using estrogen and progesterone in a substituted cycle or a natural cycle. In less common cases, gonadotropins can be used. Ultrasounds and progesterone blood tests are crucial for monitoring the growth of the endometrium and ensuring the correct timing for the biopsy.
The implantation process involves different stages, including hatching, the addition of molecules to interact with the endometrium, adhesion, and the actual inversion of the embryo into the endometrium. The success of embryo implantation depends on factors such as gamete quality (egg and sperm), endometrium status, a technique used during embryo transfer, and proper luteal phase support with appropriate progesterone levels.
To summarize, a good endometrium is vital for successful treatment. Personalizing each treatment for individual patients is crucial, and endometrial testing is a commonly used tool at Clinica Tambre to help patients with implantation failure. Studies have shown that this receptivity test improves pregnancy rates after embryo transfer and provides valuable insights into endometrial function and receptivity.
By performing a basic examination with vaginal ultrasound and utilizing endometrial tests, we can gain a better understanding of endometrial health, including the absence of infection and a favourable microbiome. The ultimate goal is to enhance reproductive outcomes, and utilizing these tools can contribute to improved success rates in personalized cases.