How the Endometrial Receptivity Array Improves IVF Outcomes

Table of Contents

• 1. Introduction
• 2. What is the Endometrial Receptivity Array (ERA)?
• 3. Who Needs the ERA Test?
• 4. How the ERA Test is Performed
• 5. ERA in Natural Frozen Embryo Transfer (Natural FET)
• 6. ERA in Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET)
• 7. Benefits of ERA for IVF Success
• 8. About Dr. Rashmi Sharma

Success of In vitro fertilization relies on the creation of a normal chromosomal embryo and the implantation of the embryo into a receptive endometrium .

In some cases when women fails to conceive even after 3 cycles of IVF then doctors begin to search for reasons why the women has been unable to conceive. Endometrial receptivity is one of the possible cause of recurrent IVF failure. This can be checked with an endometrial receptivity array test.

In 2011 the endometrial receptivity array (ERA) was first developed by Díaz-Gimeno et al. in an effort to define the transcriptomic signature of human endometrial receptivity.

Endometrial receptivity has been defined in the literature as the period of endometrial maturation during which the trophectoderm of the blastocyst can attach to the endometrial epithelial cells.

Endometrial Receptivity Array(ERA) test evaluates around 238 genes functioning that determine the endometrium receptivity. The endometrium is inner uterine lining to which the embryo must attach itself after fertilization.

Who required (Endometrial Receptivity Array) ERA test

Recurrent implantation failure :  couples who have had recurrent implantation failure otherwise good fertilization rate, the embryos have developed and appear healthy and uterine lining looks good .

 Adenomyosis : Adenomyosis may have a negative impact on endometrial receptivity, reducing the probability of conception by assisted reproductive technology .

Through molecular analyses, this impairment in endometrial receptivity has been demonstrated in part to be due to the hyperproliferation of the endometrial epithelium, impaired decidualization, progesterone resistance, altered expression  of  adhesion molecules and a hyperinflammatory microenvironment .

How to Perform Endometrial Receptivity Array (ERA)

A tissue sample of uterine endometrium is taken through biopsy .It is an outdoor procedure and it does not require anaesthesia

There are the two main available protocols for FET.

1. HRT-FET
2. Natural FET

ERA in the Context of Natural Frozen Embryo Transfer

Natural FET may be considered for women who have regular menstrual cycles .

Endometrial Receptivity Array can be used in a modified nFET cycle to better guide the timing of embryo transfer.It begins with transvaginal ultrasonography (TVUS) on days 2–3 of menses to rule out the presence of any cysts or a persistent corpus luteum from a previous cycle.  TVUS monitoring need to do continues to measure the size of the leading follicle 2 to 3 times in a cycle. Once the leading follicle has reached a diameter of 16–20 mm, hCG is given to induce ovulation. 

Endometrial biopsy is taken at hCG +7 and sent to Igenomix (Miami, FL), the medical laboratory that  analyzes the ERA .

The results of the Endometrial Receptivity Array will come back as receptive or nonreceptive. If result comes as receptive, then it represents the optimal WOI  time in the cycle and embryo transfer should be performed at the same time (±3 h) in the subsequent cycle.

Nonreceptive results are given as pre-receptive or post-receptive.

If the result is post-receptiveor  pre- receptive by 2 or more days then second ERA may be needed to validate predicted WOI in earlier Endometrial Receptivity Array assessment.  .

If the result is post-receptive then biopsy will need to be performed at LH +5 or LH +6 and if the result is pre-receptive then biopsy will need to be performed at LH +9 .

ERA in the Context of Hormone Replacement Therapy Frozen Embryo Transfer

To optimizing the endometrium for transfer Exogenous estradiol (E₂) and progesterone (P) are administered in a HRT -FET cycle at set points .

The aim of  using an Endometrial Receptivity Array is to guide the timing for an HRT-FET cycle.

A patient will  need two cycles, the first being an ERA cycle, and the second being an HRT-FET cycle . In the Endometrial Receptivity Array cycle, the patient uses the same

medications they would in an HRT-FET cycle, mimicking the uterine conditions in an eventual transfer cycle. An endometrial biopsy can be performed on day P +5 and sent for an ERA. The results of the Endometrial Receptivity Array are used to personalize the date of the embryo transfer  to the individual receptivity of each patient’s endometrium.

The ERA report shows one of three results: a receptive, pre-receptive, or post-receptive result.

If the ERA report concludes that the patient is receptive : It is considered that  the endometrium is ready for embryo transfer and in the following cycle on the day that the ERA is indicated as receptive FET is performed.

If the result is nonreceptive, then gene profile analysis results reveal whether the endometrium is pre-receptive or post-receptive. If the result states that the patient was pre-receptive then in the next cycle, a second ERA is performed on day P +6 or P +7.

If the result states that the patient was post-receptive then in the next cycle, a second ERA is performed on day P +3 or P +4.

Following the second ERA If the patient is considered receptive, then FET is performed on the same cycle day that the ERA is reported to be receptive.

https://youtu.be/1RrPNgy315k?si=YYQQxpAfEhgbkILK-

About Dr. Rashmi Sharma

Dr. Rashmi Sharma is an IVF specialist Consultant Reproductive Medicine and Director Origyn Fertility & IVF New Delhi MBBS (BHU), MD(BHU), DNB, MNAMS, FICOG, Diploma IVF and reproductive Medicine (Kiel University, Germany) Web Editor, Indian Fertility Society (2024-26) Former HOD, IVF dept, Moolchand Hospital, Delhi (2009-13) and Max Hospital, Pitampura, Delhi  (2013-17), Director, Origyn Fertility & IVF, which has 4 branches across Delhi.

Origyn IVF has been accredited for 1-year fellowship in IVF and reproductive medicine along with an MSc in Clinical Embryology under Amity University and IFS Collaboration. Recipient of the “C. S. Dawn Award” for best paper presentation on her work on IVF /ICSI with genital tuberculosis, at All India Congress Of Obstetrics and Gynecology (AICOG 2010) Recipient of “Hall of Fame – Best IVF specialist in India – North” at Economic Times – National Fertility Awards,2019 and 2023 & 2024. 

Origyn IVF received “Best IVF center in North India” and “Most integrated team in IVF, India – North” at Economic Times – National Fertility Awards, 2019 & 2024 Recipient of “Best IFS Executive” at Fertivision – 2018, Kochi. Authored various chapters in infertility books of repute. Many national and international paper presentations and publications.