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Endometrial Receptivity Analysis (ERA)

What is ERA?

Endometrial receptivity analysis, Endometrial Receptivity Array or simply ERA, is a genetic test designed to assess the receptivity of the endometrium (the lining of the uterus of a woman) during in vitro fertilization (IVF) to assess the optimal time for embryo implantation. That makes it possible for us to choose the best day to transfer the embryos during the menstrual cycle. This test is a personalized approach to determine the implantation window of a uterus that may vary from one person to another.

Endometrial Receptivity Analysis

Why ERA is so important?

Ultrasonic and microscopic techniques enable us to appreciate many characteristics of the endometrium, like its thickness, cellular growth, and gland development. However, these direct observational techniques do not provide accurate estimation for receptivity. Thus, ERA is a crucial test in assisted reproductive technology, especially for those with a previous history of multiple implantation failures.

Understanding Endometrial Receptivity

The endometrium is the mucous layer that lines the internal walls of the uterus. Under the influence of sex hormones, it undergoes many changes during the menstrual cycle and gets ready for embryo implantation. Endometrial receptivity is the ability of the uterus to interact with the embryo so that implantation may occur. This ability continuously changes during the menstrual cycle, and the time when this ability is maximum is called the implantation window. During this time, the endometrium attains the ideal environment and full acceptability for the embryo. Knowing about this time precisely is what we call endometrial receptivity analysis.
ERA-Endometrial Receptivity Analysis Test

Factors Influencing Endometrial Receptivity

Hormonal Regulation:
The role of sex hormones, especially estrogen (or estradiol) and progesterone, in endometrial receptivity is pivotal for successful embryo implantation during the menstrual cycle. Estrogen increases the thickness and vascularity of the endometrium. Progesterone promotes the development of endometrial glands, which secrete nutrients and create an optimal environment for embryo attachment. It also inhibits premature uterine contractions, ensuring the embryo remains attached in place. The endometrium undergoes simultaneous morphological and functional changes brought about by both hormones, creating the perfect environment for embryo implantation.
Molecular Signaling Pathways:

Many signaling pathways participate in achieving optimal receptivity of the endometrium. For instance,

  • STAT3 (Signal Transducer and Activator of Transcription 3), LIF (leukemia inhibitory factor), Ihh (Indian Hedgehog) signaling, and BMP (bone morphogenetic protein); all these factors promote endometrial growth and lead to the necessary morphological and functional achievements for successful implantation.
  • Cytokines like interleukins, TNF-α (tumor necrosis factor), and TGF-β (tumor growth factor) regulate immune cell activity, formation of new vessels, and remodeling during menstruation and implantation.
  • Insulin and Insulin-Like Growth Factor (IGF) Pathways regulate endometrial growth and differentiation.

The impact of Uterine pathologies

Numerous uterine diseases can interfere with the endometrium’s receptivity and the smoothness of the implantation process. The following factors can impair endometrial receptivity, leading to adverse reproductive health events, including infertility and miscarriage
  • Uterine polyps are abnormal growths in the endometrium
  • Uterine fibroids are non-cancerous tumors of the uterine muscle.
  • Adenomyosis is a condition where endometrial tissue grows into the uterine muscles
  • Chronic Endometritis is long-term inflammation of the endometrium
  • Polycystic Ovary Syndrome (PCOS) affects hormonal balance and causes cycle irregularities
  • Infections (such as sexually transmitted infections) can also disrupt the endometrium receptivity

The procedure of endometrial receptivity analysis

The most used technique for the ERA test is taking an endometrial tissue biopsy. Either the patient undergoes a standard round of hormone replacement therapy or, in the case of a natural cycle, simply the theoretical time of receptivity is calculated (from LH surge). At that time in the menstrual cycle, the biopsy is taken instead of transferring a frozen embryo. The endometrial lining is scratched to obtain a tissue biopsy sample, which is then kept in a sterile container with strict temperature protocols and sent to the lab for genetic sequencing. Although it may cause some discomfort at the time, it is a minimally invasive procedure where general anesthesia and operation theatre are required only in exceptional cases like for patients with cervical stenosis (narrowing of the pathway used for biopsy). The patient can also request general anesthesia.

Interpretation of ERA Results

The researchers have identified more than 200 genes associated with receptivity and implantation and categorized the results in 3 different ways.
  • Pre-receptive: The patient’s gene-expression profile matches the endometrium’s pre-receptive stage. This period is too early for embryo transfer.
  • Receptive: The gene-expression profile of the patient corresponds with the implantation window. It is the best period for embryo transfer and will provide maximum chances of implantation.
  • Post-receptive: The patient’s gene-expression profile is consistent with the endometrium’s post-receptive stage. This period is too late for embryo transfer.
These results help the doctor to find the receptivity window of every patient. The doctor schedules and customizes the embryo transfer to maximize the chances of a successful pregnancy.

ERA & Assisted Reproductive Technologies (ART)

Since the inception of assisted reproductive techniques, the embryo has remained the central focus. In contrast, the maternal endometrium was considered a passive part of the reproductive process. Only good quality and maximum number of embryos mattered. Thus, the efficacy of IVF treatment remained very low.
Personalized Embryo Transfer (PET) guided by ERA has better results for pregnancy and implantation than Frozen Embryo Transfer (FET).

Assisted-Reproductive-Technology (ART)

Who should consider the ERA Test?

The majority of women undergoing IVF treatment for infertility who stand to benefit from the ERA test are those who, while having high-quality embryos, have experienced several unsuccessful embryo implantation attempts.
Choosing the right IVF center is decisive in the treatment of infertility couples. Any center with experienced IVF specialists, state-of-the-art embryology laboratories, and a highly qualified and professional team of embryologists practicing advanced techniques and covering maximum geographic locations would be the best choice. Australian Concept Infertility Medical Center is state-of-the-art fertility clinic in Pakistan.

Cost of Endometrial Receptivity Analysis

Different conditions, such as healthcare providers, current inflation/taxes, and additional services, can cause the cost to vary. However, the ERA test is worth the money because it gives essential information about endometrial receptivity during IVF. 30% of IVF cycles fail due to embryo transfer outside the window of receptivity.

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