Implantation failure is a cause of anguish & heartache for couples who wish to become parents. There are various reasons why the implantation process can be unsuccessful.
There is no single universally accepted definition of Recurrent Implantation Failure (RIF), because of the variation in the ways it is determined by different medical practitioners. We will look at these root causes and also look at potential treatments in this article.
In This Article
- What is Implantation Failure or Recurrent Implantation Failure?
- What are the Causes of Implantation Failure in IVF or In Vitro Fertilization?
- What Tests are Conducted to Identify the Cause of Implantation Failure?
- What are the Suggestive Treatments & Alternatives after Recurrent Implantation Failure?
What is Implantation Failure or Recurrent Implantation Failure?
Let’s begin by understanding what is meant by ‘successful embryo implantation’ first. Successful Embryo Implantation is a process that holds good these given points:
- Synchronous development
- Interaction between hatched blastocyst and endometrium.
- The gestational sac is diagnosed by ultrasound.
And, ‘Implantation Failure’, is the term used to refer to the situation, where:
- No implantation took place at all, or
- Implantation did take place. but there was nothing to be diagnosed by ultrasound. In other words, the process beyond the formation of the gestational sac stopped.
Recurrent implantation failure’s definition, however, encompasses two essentials:
- The number of embryos transferred
- The number of ET or embryo transfer procedures conducted
Approximately twenty years ago recurrent implantation failure was defined as the one in which there were more than twelve embryo transfers but, all with a failed pregnancy. This definition was, however, modified because it undertook the frozen embryo transfers too (which had a pregnancy rate very low). The new definition thus considers fresh embryo transfers only. So three recurrent failed pregnancies after more than three fresh embryo transfers (good quality embryos) are termed a recurrent implantation failure.
What are the Causes of Implantation Failure in IVF or In Vitro Fertilization?
Few definitions for recurrent implantation failure necessarily encompass the presence of ART or assisted reproductive technology for pregnancy. And in such cases, RIF is defined as the failure of clinical pregnancy even after the transfer of four good-quality embryos in women who are not above the age of forty years. These four embryo transfers need to have a minimum of three fresh or frozen IVF cycles.
IVF or in vitro fertilization, though it seems like an option to get pregnant through medical means, does not guarantee a hundred percent success rate. In spite of the advancement in science and technology, the interdependence on natural factors does affect the guarantee of getting pregnant through IVF. So if you are planning to get an IVF done, give it a second thought after considering the below-mentioned factors, only.
Reasons for Implantation Failure
The top reasons for implantation failure are:
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Maternal Age
It is true that with growing age the quality of eggs of a woman tends to deteriorate. And this does affect the success rate of getting pregnant even in the case of IVF. The age of the patient at the time of oocyte collection (Oocyte collection or transvaginal oocyte retrieval (TVOR), or oocyte retrieval (OCR), is a method used in in vitro fertilization (IVF) to get the oocytes from the ovary of a woman, thus enabling fertilization even outside the body) and freezing are the main determining factor for getting pregnant biochemically. So it is concluded that pregnancy success is affected by both the quality of the embryo and the age of the mother both.
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Embryo Competency or Quality
Embryos generated out of the eggs from aging mothers are of poor genetic quality and might have the wrong number of chromosomes and incorrect or insufficient genetic information. Such embryos are either incompetent or of poor quality to support a successful pregnancy, thus leading to early miscarriages. If in the rarest of the cases pregnancy turns out to be successful, the baby may suffer from genetic disturbances.
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BMI
Body mass index (BMI) is the measurement of body fat in an adult male or female on the basis of height and weight. BMI above 25 does have a negative effect on the success rate of IVF. Additionally, overweight and obese women with lower oocyte collection have a high rate of pregnancy failure.
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Role of the Endometrium
During IVF, the endometrial receptivity is identified with the help of ultrasound images. Endometrial thickness is thus measured using the images taken from the ultrasound. For successful embryo transfer, an endometrium should be greater than 8mm. The endometrium becomes receptive only after progesterone exposure, which brings about necessary changes in the endometrium to accept the embryo. Frozen embryo transfers are more successful than fresh embryo transfers in IVF.
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Non-Receptive Uterus
Uteruses that contain adhesions, fibroids, or polyps in the cavity have decreased receptivity. If there is an increase in progesterone levels before egg collection during an IVF cycle, then also the receptivity of the uterus for embryo transfer is not a click. This, therefore, leads to failed implantation.
An infection of the uterus makes the uterine environment less optimal for proper implantation. Other immunological factors also add like the presence of a high number of uterine NK cells, excessive HLA matching between the couple, and the issue of blood clotting.
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Smoking
Although there is no derived evidence to confirm that smoking does lead to failure in pregnancy attempted through IVF, it has been significantly observed that implantation failure in women who smoke is more as compared to non-smokers. The level of toxins in cigarettes plays a role in disrupting the implantation of the embryo and corpus luteum formation.
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Stress
Stress is one of the most common root causes of almost all personal and professional failures in life. Stay away from it. As per a study, stress and implantation failure are very common risk factors associated with each other. At the time of stress, the stress hormone termed cortisol tends to increase above its normal level, thus leading to failed pregnancy within the first three weeks of getting pregnant.
In the case of IVF pregnancy, the first-time IVF anxiety or stress does not seem to negatively impact the success rate. But those who suffered failed IVF initially, do carry a high level of stress in their trials post-failure. And stress during this time is not acceptable at all.
What Tests are Conducted to Identify the Cause of Implantation Failure?
Implantation failure or recurrent implantation failure is not a permanent disorder. By proper identification of the implantation failure reasons, the problem can be solved. But what are these clinical tests that can help identify the reason for failed pregnancies? Let’s study!
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Uterine Evaluation/Hysterosalpingogram (HSG)
When an IVF is to be conducted, the status of the fallopian tubes is to be properly observed. The tubes need to be clear because blocked tubes reduce the success rate of pregnancy by almost fifty percent. To know the status of the tubes and the uterus, one needs to conduct the uterine evaluation test or hysterosalpingogram (HSG) test.
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Sperm DNA Fragmentation Test
A sperm DNA fragmentation test, as the name suggests, is done to study the level of DNA fragmentation in the sperm. A high level of DNA fragmentation results in a lower fertilization rate, a lower rate of successful implantation, and an increased level of miscarriage.
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Endometrial Receptivity Assay (ERA)
An endometrial receptivity assay or ERA test is conducted to conceptualize the receptivity of the endometrium for implantation. In this test, the biopsy of the endometrium is done. If the endometrium is not perfect for implantation on a particular day, then the embryo transfer can be done a day ahead or a day later.
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Preimplantation Genetic Testing for Aneuploidy (PGT-A)
We have studied earlier that incompatible embryos or embryos with the wrong number of chromosomes result in failed conception or abnormal births or miscarriages. In Preimplantation Genetic Testing for Aneuploidy (PGT-A), cells are removed from a developing embryo and then are tested for their chromosome content. Embryos with a normal complement of chromosomes are chosen for embryo transfer, thus leading to improved pregnancy. In today’s modern times, this PGT-A is considered to be a wise option for improving the pregnancy with a single embryo only.
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Immunologic Tests
Immunological tests are both expensive and controversial. The controversy is because of the lack of data for conducting tests and proposed treatments to treat the immunologic abnormalities. The immunologic test is therefore taken as the last resort when even after all remedies, a woman fails to get pregnant.
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Intracytoplasmic Morphological Sperm Injection (IMSI)
The Intracytoplasmic morphological sperm injection (IMSI) test is done to identify if there are any tiny defects in the sperm head that might have gone undetected during DNA testing.
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Karyotype
A karyotype is a blood test done to check the genetic variations that might be causing implantation failure.
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Thrombophilia (clotting) Screen
Thrombophilia screening is done to identify any genetic reasons which might lead to blood clotting thus resulting in implantation failure.
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Immunology Screening
The immunology screening is done to measure the presence of white blood cells, which when increased tend to adversely impact the implanted embryo.
What are the Suggestive Treatments & Alternatives after Recurrent Implantation Failure?
Once the reasons for recurrent implantation failure are identified by means of the tests discussed in the above section, the respective list of treatments follows:
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Preimplantation Genetic Diagnosis (PGD)
Preimplantation genetic diagnosis(PGD) is the treatment applied in the case of women with chromosomally inappropriate embryos or women who desire to attain pregnancy at the age of thirty-five years. In this process, the morphologically good-quality embryos are chosen in a reproduction lab for implantation. Such treatment is also effective in the case of parents with altered karyotypes.
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Extended Culture to Blastocyst
Extended culture to blastocyst treatment requires keeping the embryos in vitro culture for 5 days, till the blastocyst stage. Embryo transfer is done thereafter post day 5 instead of day 3.
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Surgical Techniques
Surgical techniques are effective in cases where the cause of implantation failure is alterations in the structure of the uterus or blocked fallopian tubes. In the case of blocked tubes, a bilateral salpingectomy is done to remove the fluid from the tubes, thus improving the chance of getting pregnant. Laparoscopy or hysteroscopy is done when there are septa, polyps, or fibroids in the uterus cavity. Endometrial scratching is a surgical technique to renew the endometrium and increase the chances of getting a successful pregnancy.
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Endometrial Receptivity Analysis (ERA):
The Endometrial Receptivity Array (ERA) is a diagnostic test as well as a treatment technique to identify the abnormality in the implantation window and vitrify the embryos to transfer them when there is maximum endometrial receptivity.
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Pharmacological Treatment:
If endocrine alterations, immune alterations, and thrombophilic factors are shown as the reasons for implantation failure, then medicines like aspirin and heparin are very effective. Such medicine treatments are to last throughout the pregnancy until the baby is born. In the case of a female reproductive system fault, it is advisable to perform the treatment with antibiotics. This will ensure that the uterus is not inflamed and the endometrial receptivity is perfect.
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Egg and Embryo Donation:
Egg and embryo donation is a considerable option when the embryonic result is not positive. In the case of elderly women, egg donation treatment offers very good results. Sperm donation is a good option if the fault is in the sperm of the to-be-father.
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Surrogacy:
Often each and every piece of medical advice fails, and the result is only stress and depression. At this moment, surrogacy is the last resort. Surrogacy is an assisted reproduction technique where the fertilized IVF embryos of the to-be parents are transferred into a healthy woman, who is called a surrogate. A surrogate mother takes the charge of gestation of the baby throughout the pregnancy.
Recurrent implantation failure can occur because of reasons under your personal control or because of reasons beyond your control. It can happen in the case of both natural pregnancy and in IVF treatments. So it is better to educate yourself completely with entire information on implantation failure symptoms, reasons, and treatments, before coming to any final decision.
