Endometrial Receptivity Analysis or ERA test is a test used to assess the uterine lining receptivity in women who have experienced multiple unsuccessful attempts to conceive. By analyzing the optimal time with maximum chances of embryo implantation during IVF,, this test can help to determine the optimal timing for embryo transfer, thus increasing the likelihood of successful pregnancy in women with recurrent miscarriage.

Understanding the cause for repeated failure of pregnancy

Couples who experience repeated pregnancy failures can find themselves in a difficult and emotionally taxing situation. Repeated failure of pregnancy can be attributed to a variety of factors such as:

Chromosomal abnormalities: Chromosomal abnormalities in the egg or sperm can result in early miscarriages, as well as structural problems in the uterus, including fibroids and polyps, which may impede implantation or result in complications during pregnancy. Furthermore, hormonal imbalances, such as thyroid disorders or Polycystic Ovary Syndrome (PCOS), can affect fertility and lead to recurrent pregnancy loss.

Autoimmune disorders: In autoimmune disorders, the immune system mistakenly attacks the embryo. In conditions such as thrombophilia, the risk of blood clot formation increases and the blood supply to the placenta is impaired, leading to miscarriage.

Lifestyle factors: Factors including smoking, heavy drinking, and being overweight or underweight can have a negative effect on fertility and increase the likelihood of having multiple unsuccessful pregnancies. Advanced maternal age plays an important role as women over 35 have a higher incidence of chromosome abnormalities in their eggs.

Genetic factors and familial predisposition: Genetic mutations may also influence the occurrence of repeated abortions.

What is The Window of Receptivity?

The uterine receptivity window is a brief period of time in the menstrual cycle during which the lining of uterus is optimally prepared for receiving the embryo, leading to successful pregnancy.

During this window, the endometrium undergoes certain changes to become more receptive to the incoming embryo. The blood flow to the uterus increases and the inner lining of the uterus produces certain chemicals which favor successful pregnancy.

Window of implantation is around day 20 of a 28 day cycle. It lasts for 3-4 days.. It may, however, vary for women with longer or shorter cycles.If the uterus is exposed to a healthy embryo at this time, pregnancy happens.

In IVF, the embryo is transferred back into the uterus at this time with maximum chances of successful implantation. Endometrial Receptivity Analysis (ERA) test has revolutionized the process of determining the time of maximum implantation potential of the uterus, thus enhancing the likelihood of successful pregnancy for couples with fertility issues.

How does the ERA test work?

The Endometrial Receptivity Analysis (ERA) test is used to assess the optimal window of endometrial receptivity for embryo implantation during assisted reproductive procedures, such as in vitro fertilization (IVF).  

The ERA test involves a series of steps:

Endometrial biopsy: A uterine biopsy is performed during a woman’s natural cycle or hormone replacement cycle. A thin catheter is used to collect a small sample of the uterine lining. The collection of the uterine biopsy occurs 7 days after the luteinizing hormone (LH) surge during a natural cycle.

Molecular analysis: The tissue sample collected is then analyzed for the expression of 248 genes that are involved in the development of endometrium receptivity. The gene expression profile is used to determine if the endometrium is “receptive” or “not-receptive” at that particular time.

Personalized timing: The ERA test utilizes gene expression data to determine when the endometrium is most receptive for each individual.

Treatment adjustment: Embryo transfer during assisted reproductive procedures can now be tailored to the patient’s particular window of receptivity, thus increasing the likelihood of successful pregnancy. This personalized approach ensures that the embryo is inserted into the uterine lining at its most receptive point.

The ERA test represents a significant advancement in assisted reproductive technology, offering a personalized approach to time the embryo transfer, correctly. By analyzing the molecular status of the endometrial lining, it helps identify the precise window of implantation for each individual. This tailored approach holds promise for couples facing recurrent pregnancy failures, as it maximizes the chances of a successful pregnancy.

NU Fertility at NU Hospitals, based in Bangalore, provides modern treatment options for women suffering from recurrent pregnancy loss. The doctors at NU Fertility have many years of experience in the field of reproductive health and are trained to handle even the most sensitive cases with expertise and precision. If you want to know more about ERA testing, get in touch with NU fertility specialists.

References:

1.     Mahajan N. (2015). Endometrial receptivity array: Clinical application. Journal of human reproductive sciences, 8(3), 121–129. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601169/.
2.  Recurrent pregnancy loss. UCLA HEALTH. https://www.uclahealth.org/medical-services/obgyn/conditions-treated/recurrent-pregnancy-loss.
3.   Understanding Repeated Pregnancy Loss. Stanford Medicine. https://www.stanfordchildrens.org/en/topic/default?id=understanding-repeated-pregnancy-loss-1-2074.
4.  Liu, Z., Liu, X., Wang, M., et al. (2022). The Clinical Efficacy of Personalized Embryo Transfer Guided by the Endometrial Receptivity Array/Analysis on IVF/ICSI Outcomes: A Systematic Review and Meta-Analysis. Frontiers in physiology, 13, 841437. https://pubmed.ncbi.nlm.nih.gov/35574479/.

Author: Dr. Sneha J

An embryo transfer is the first step of in vitro fertilization (IVF). Embryo transfer involves the fertilization of eggs outside the body and the transfer of the embryos into the uterus to achieve a pregnancy. Preparing for embryo transfer is a crucial step in the journey of assisted reproductive technology (ART). Proper preparation is essential to maximize the chances of a successful pregnancy. In this blog, we will explore the steps to prepare for embryo transfer, covering various aspects to ensure a smooth and successful procedure.

Indications for Embryo Transfer

Embryo transfer is a critical procedure in the field of reproductive medicine, typically recommended for various conditions that hinder natural conception or pose risks during pregnancy. Common indications for embryo transfer include:

Infertility: When couples struggle to conceive due to factors such as male or female infertility, embryo transfer can help by placing healthy embryos into the woman’s uterus.

Recurrent Pregnancy Loss: For individuals experiencing multiple miscarriages, embryo transfer may increase the chances of a successful pregnancy by selecting the healthiest embryos.

Medical Conditions: Certain medical conditions, such as uterine abnormalities or previous surgeries, can affect a woman’s ability to conceive or maintain a pregnancy. Embryo transfer can overcome these obstacles.

Single Parent: Embryo transfer allows women to have biological children by using donor sperm.

Age-Related Fertility Decline: As women age, their fertility decreases. Embryo transfer with younger, healthier embryos can improve the chances of a successful pregnancy in older women.

Preparation for Embryo Transfer

Preparing for embryo transfer involves a combination of physical, emotional, and logistical considerations. Here are the steps you need to take to get ready for an embryo transfer:

Consultation and Planning: Start your preparation by choosing a reputable fertility clinic or ART centre having experienced professionals. Schedule a consultation with a fertility specialist to discuss your individual situation and treatment plan. The specialist will review your medical history and assess any potential factors affecting fertility.

Preparing your Body: Begin adopting a healthy lifestyle by eating a balanced diet, exercising regularly, and avoiding alcohol and smoking. Follow your doctor’s advice on taking specific prenatal vitamins and supplements, such as folic acid, to support pregnancy. Comply with prescribed medications, such as hormonal injections, to prepare the uterine lining for embryo implantation.

Synchronization of Cycles: If you are using a donor egg or sperm, ensure synchronization of cycles with the donor. Take hormonal medications as per your doctor’s instructions to align your menstrual cycle with the embryo’s development.

Psychological Readiness: Consider seeking counselling or psychological support to manage the emotional stress associated with fertility treatments. Lean on your support network, including friends and family, to provide emotional assistance during this process.

Pretransfer Tests: Undergoing an ultrasound to evaluate the uterine lining’s thickness and structure and blood tests may be required to check hormone levels and overall health before proceeding.

Lifestyle Adjustments: Practice stress reduction techniques such as yoga, meditation, or deep breathing exercises to help relax your body and mind. Consider adjusting your work schedule to accommodate medical appointments and potential rest periods after the transfer.

Pretransfer Instructions: Stay well hydrated in the days leading up to the embryo transfer. Avoid or limit caffeine and alcohol consumption. Refrain from sexual activity a few days before the embryo transfer. Maintain good personal hygiene to prevent infections and wear loose, comfortable clothing on the day of the transfer. Make sure you have reliable transportation to and from the clinic on the day of the transfer. Consider having a companion accompany you for support and assistance.

Understanding the Procedure: Take time to understand the embryo transfer procedure, what to expect, and any potential risks or complications involved. Ask your doctor any questions or concerns you may have about the process.

The day of the Embryo Transfer: Arrive at the clinic on time, allowing for any necessary paperwork and preparation. Listen carefully to the medical team’s instructions and explanations of the procedure.

Post Transfer Care

Plan to rest for the remainder of the day following the transfer. Avoid strenuous activities and lifting heavy objects. Continue any prescribed medications and follow-up appointments. The two-week waiting period after the transfer can be challenging. Stay patient and avoid taking home pregnancy tests prematurely. Follow-up appointments to check for pregnancy are essential during this phase.

To summarize briefly, embryo transfer is a versatile and effective method for overcoming various reproductive challenges, enabling individuals and couples to achieve their dream of parenthood. With proper planning and working closely with your fertility specialist, you can increase your chances of a successful embryo transfer and, ultimately, a healthy pregnancy.  

NU Fertility Hospitals in Bangalore, India is renowned as one of India’s premier infertility centres, excelling in embryo transfers. With cutting-edge technology, a highly skilled medical team, and a strong track record of successful pregnancies, it stands out as the first choice of individuals and couples seeking advanced reproductive solutions.

References:

1.    Embryo Transfer. American Pregnancy Association.https://fertility.nm.org/ovulation-induction.html.
2.    Embryo Transfer. Cambridge IVF. https://www.stanfordchildrens.org/en/service/fertility-and-reproductive-health/ovulation-induction.
3.    Embryo Transfer. Stanford Medicine. https://www.ucsfhealth.org/education/ovulation-     induction.

Author: Dr. Sneha J

Infertility in women may be caused due to several reasons. Many a times, it is caused by ovulation problems. Ovulation is the process of release of a mature egg from the ovary. Under normal circumstances, the released egg travels to the fallopian tube where it gets fertilized by a sperm. Over a period of several days, the fertilized egg travels to the uterus, where it gets implanted. When this happens, a woman is said to be pregnant.

What is ovulation induction (OI)?

Ovulation induction is a method of assisted reproduction, useful for treating fertility issues in women who either do not have a normal ovulation or have no ovulation at all owing to hormonal disorders or a condition called Polycystic Ovary Syndrome (PCOS). In OI, fertility medications are used to stimulate the release of one or more eggs from the ovary.

Need for OI

Generally, OI is done in one of two particular situations. Firstly, it is brought to use in conditions where the woman has irregular menstrual cycles and does not release an egg on her own to ovulate. With the help of these medications, the woman is able to release a single egg. Secondly, OI is helpful even if the woman is ovulating regularly on her own. In such a situation, these medications are used with an aim to release several eggs at a time. The idea behind this is that a couple who is unable to achieve pregnancy with the woman just releasing one egg per month, the chances of getting pregnant will increase if 2-3 eggs are released at a time.

How does OI work?

Ovulation-inducing medications are often the first line of treatment your healthcare provider will try in order to achieve pregnancy. These medications belong to a class called gonadotropins and work by stimulating the release of hormones that facilitate egg production. Basically, there are two types of OI medications:

1.     Oral medications: Often treated as the first line of treatment, these medications help women who do not ovulate or ovulate infrequently. As part of the treatment, first an ultrasound and some blood tests are carried out on the second or third day of the menstrual cycle. Starting from day 2-5 of the cycle,, you will be given oral medications such as clomiphene or letrozole for 5 days . Following this, a vaginal ultrasound will be performed on the 10th or 11th day to check how well the egg has developed. With the help of an ultrasound and blood tests, your healthcare provider would be able to monitor the development of follicles, based on which you may start attempting to conceive naturally or through intrauterine insemination (IUI).
2. Injectable medications: In case oral medications are unsuccessful in giving the desired results, injectable medications containing hormones such as follicle-stimulating hormone (FSH) and Leutenizing hormone (LH) may be administered. As with oral medications, the treatment cycle begins with an ultrasound and blood tests on day 2-3 of the menstrual cycle. The injectable medications are then administered in the first half of the menstrual cycle, depending upon the response. When the lead follicle/s measure at least 16-18mm in diameter, you will be injected with human chorionic gonadotropin (hCG) to trigger ovulation. At this juncture, intercourse or IUI can be performed. This fertility medication (hCG) can be used with both IUI and IVF.

Success rate of ovulation induction

The rate of success of OI depends on the woman’s diagnosis and other factors, particularly her age. Up to 20-25% of success rate of pregnancy per cycle can be achieved in young, healthy couples with no fertility issues. 

Keeping in mind the various advancements that have taken place in the field of fertility medicines, a couple need not lose hope of achieving pregnancy. With the right approach and medical aid, the dream of becoming parents can be fulfilled. Ovulation induction is the answer for many childless couples who are dealing with infertility issues.

NU Fertility @NU Hospitals offers the best treatments available to deal with infertility issues. It is the best ovulation induction fertility treatment hospital in Bangalore. The team of fertility experts here work day in and day out to help you achieve pregnancy at the earliest. As a couple who is facing fertility issues, you can visit NU fertility center and get yourself treated for the same. Giving a new lease of hope and life is the motto of NU Fertility @ NU Hospitals, Bangalore.

References:

1.   Ovulation induction. Northwestern Medicine. https://fertility.nm.org/ovulation-induction.html.
2.   Ovulation induction (OI). Stanford Medicine Children’s Health. https://www.stanfordchildrens.org/en/service/fertility-and-reproductive-health/ovulation-induction.
3. Ovulation induction. Patient education. University of California San Francisco (UCSF Health). https://www.ucsfhealth.org/education/ovulation-induction.
4. Ovulation Induction and Intrauterine Insemination. Yale Medicine. https://www.yalemedicine.org/conditions/ovulation-induction-intrauterine-insemination.

Author: Dr. Sneha J

In this case study, we witness a case of a 33-year-old woman who despite having a birth defect, was still able to conceive. Surgical removal of the defect almost stopped her menstrual cycle. Later, she was counseled for fertility treatment and after undergoing it, she cherished the much-desired pregnancy.

Two years ago, 33-year-old Kavita (name changed for privacy) had undergone surgery for a septate uterus at another hospital.

A septate uterus is a layer of fibrous tissue splitting the uterine cavity into two halves. Some people are born with a septate uterus, and they may not know it until they undergo a test for infertility, frequent abortions, or occasionally while doing a caesarean section, as an incidental finding. This is a birth defect seen in 2-3% of women.

Impact of PCOS on Fertility

Owing to this surgery, her menstrual bleeding declined drastically. Before surgery, there were 4-5 days of bleeding every month, which after surgery got reduced to only spotting on the first day of periods.

She explained this worrisome situation to Dr. Sneha, a Fertility Specialist at NU Fertility, Bengaluru, which stressed her out as she desired to become a parent. So, a diagnosis of “Asherman Syndrome” was made as it is seen in 2% of women after this kind of surgery.

Asherman Syndrome is a condition wherein dense adhesions inside the uterus cause decreased space and blood flow for the prospective fetus to grow.

Further, in view of the severely decreased sperm count in her husband (Oligoasthenoteratospermia), she was counselled for Intracytoplasmic Sperm Injection (ICSI) as well as In-vitro Fertilization (IVF).
Medications for stimulation of follicle growth in the ovaries were given, egg retrieval was done, and 6 good-quality embryos were frozen on day 4.

Soon, she had to undergo treatment for the adhesions in the uterus if IVF/ICSI had to work. She underwent hysteroscopy (introduction of a camera to inspect the inside of the uterus) and removal of adhesions inside in 2 sittings, 1 month apart.

The menstrual blood flow improved to 1-2 days of decreased flow in the subsequent cycle. She was happy that she was bleeding again during her cycle, though not like before.

Her embryo transfer was planned in a natural cycle after 5 months, giving adequate time for the uterus to heal to harbor a healthy pregnancy. The uterine lining was not adequate and embryo transfer had to be cancelled for two consecutive months.

We used the latest technique of injecting Platelet-rich plasma (PRP) into the uterine cavity to improve the uterine lining to house the embryo and allow its successful growth. PRP acts by increasing growth factors in the uterus. The uterine lining grew to 5mm which is still below the standard proposed- 7mm. After explaining the chances of embryo implantation, we transferred 2 embryos into the uterus.

A good thick uterine lining is required for success in an IVF /ICSI cycle as this provides space and nutrition to the developing embryo.

The biggest surprise was when her pregnancy test turned positive. Scanning at 6 weeks showed that both the embryos implanted in the uterus, and one had a heartbeat too. The other fetus stopped growing, confirmed on the 8-week scan.

Subsequent follow-up sessions showed that she was 10 weeks pregnant with a normal-growing fetus inside.
If you have a septate uterus and you desire to have a baby, you should talk to your infertility specialist about the possible treatment options.

Having a septate uterus does not mean you cannot have a baby. It just means you may need some extra care and support along the way. With proper treatment and guidance, you can have a successful pregnancy and a healthy baby.

Key Takeaway:

• Septate uterus is a congenital malformation that shows no symptoms most of the time. Further, it does not always have an effect on fertility.
• However, if it causes hindrance to fertility or pregnancy, it may be surgically removed after a thorough diagnosis by a fertility doctor.
• Septal resection is a commonly performed procedure with good results. About 60% of women conceive naturally after septal resection if this is the cause of infertility.
• Complications can happen with any procedure in medicine, and there are ways to tackle them.

Polycystic ovarian syndrome (PCOS) is a health condition that affects women of childbearing age. In this condition, the ovaries tend to produce excess androgens, a male sex hormone that is usually present in small amounts in women. The name, polycystic ovarian syndrome, describes numerous small cysts (fluid-filled sacs) in the ovaries. However, these are different from the other ovarian cysts which require surgery. PCOS can have an impact on a woman’s overall health as well as their physical appearance. Although common, PCOS is often a treatable condition.

Impact of PCOS on Fertility

Hormonal imbalances in women may result in excessive amounts of androgens, the formation of cysts in the ovaries, the thickening of the outer well of the ovaries, and insulin resistance. All these changes can interfere with the process of ovulation in women. One of the common signs to understand this is missed or irregular periods.

Signs and symptoms

The symptoms of PCOS may include:

• Missed or irregular periods
• Infertility
• Skin tags
• Acne or oily skin
• Ovaries that are large or have several cysts
• Excess body hair (hirsutism)
• Male pattern baldness or thinning of hair
• Dark or thick skin patches at the back of the neck, in the armpits, and under the breast

Causes

The exact cause of PCOS still remains unclear. However, it has been shown that most women with PCOS have insulin resistance, which means their bodies cannot utilize insulin effectively. Accumulated insulin levels in the body lead to potential rise in androgen levels. Obesity can also raise insulin levels, worsening PCOS symptoms.

Diagnosis

PCOS is diagnosed in the following ways:
To begin with, your healthcare provider will take your complete medical history along with your symptoms. Following that, you will have to undergo a thorough physical examination, especially of the pelvic region. This includes checking the reproductive organs closely.
A few additional tests may also be ordered to confirm the diagnosis. These include:
Pelvic ultrasound: This test creates images of blood arteries, tissues, and organs using sound waves and a computer. It examines the size of the ovaries as well as the presence of cysts in them. It also provides information on the thickness of the endometrium (inner lining of the uterus).
Blood tests: These tests provide information on the levels of androgen and other hormones in women. Additionally, it may provide information on blood glucose, cholesterol, and thyroid levels.

Treatment

There is no treatment available for PCOS as such. However, the symptoms can be treated and managed well. Infertility treatment caused by PCOS involves correcting ovulation issues and tackling metabolic problems, such as insulin resistance. If you have a BMI of 30 or above, your healthcare professional may advise you to lose weight by adopting a healthy eating pattern and regular exercise.
If you don’t wish to become pregnant, hormonal birth control pills may be helpful. However, a few treatments that may help you ovulate and conceive include:
Medicines that stimulate ovulation (releasing an egg)
These medications work by stimulating the ovary to grow eggs. These are taken once a day for five days at the start of your menstrual cycle.
These drugs work quite effectively in helping women with PCOS to ovulate. However, these are started at the lowest possible dose and increased as needed, by your healthcare practitioner.
Insulin-sensitizing drugs
These medications are effective in women with insulin resistance – a condition where insulin fails to act in the body. These drugs aren’t first-line treatments for PCOS but can be used to encourage regular periods and ovulation. They may not be as effective as other treatments of PCOS in helping women to become pregnant but can stimulate ovulation.
Hormone injections
These are injectable hormones that facilitate ovarian stimulation and ovulation. This treatment may require frequent doctor visits to monitor your body’s response to the drug.
Surgery
Surgery in the form of laparoscopic ovarian drilling is recommended for patients who do not respond to medications. Although rare, it may be an option.

Complications of PCOS

If left untreated, women with PCOS may be likely to develop serious health conditions such as

• Type 2 diabetes mellitus
• High blood pressure
• Heart diseases
• Sleep disorders
• Depression and anxiety
• Infertility
• Uterine cancer

PCOS is a common hormonal problem in women of childbearing age these days. It affects the menstrual cycle and causes many symptoms. It is best to speak with a healthcare provider if you believe you are experiencing any PCOS-related symptoms. You can control the symptoms, reduce risk factors, and increase your chances of getting pregnant with the help of medical interventions and lifestyle modifications.
NU Hospitals located in Bangalore, India provides special effective treatment for PCOS by well-trained doctors to handle even the most delicate cases with expertise. If you are suffering from PCOS, or have any queries related to infertility, consult the specialist at NU Hospitals today!

References:

1. PCOS and fertility. Tommy’s. https://www.tommys.org/pregnancy-information/planning-a-pregnancy/fertility-and-causes-of-infertility/pcos-and-fertility-everything-you-need-know. Accessed on 28 September 2023.
2. Polycystic ovarian syndrome. OASH | Office on Women’s Health. https://www.womenshealth.gov/a-z-topics/polycystic-ovary-syndrome#:~:text=Having%20PCOS%20does%20not%20mean,you%20can’t%20get%20pregnant. Accessed on 28 September 2023.
3. PCOS and pregnancy. Pregnancy birth & baby. https://www.pregnancybirthbaby.org.au/pcos-and-pregnancy. Accessed on 28 September 2023.

Author: Dr. Sneha J