Couples facing fertility problems may be recommended to opt for Assisted Reproductive Technology (ART) solutions. One such ART solution is called IVF or In-vitro Fertilization. In this procedure, sperms and eggs from the male and female partners respectively are made to fertilize under laboratory conditions. Through this procedure, one can bypass the sperm’s movement through the cervix to the fallopian tube and thus gives a better chance at fertilization for those couples who are facing severe male factor infertility or cervical mucus related problems. However, despite this, the IVF procedure has a success rate of about 40% which may reduce with an increase in maternal age. Repeated IVF failures lead to a feeling of disappointment, hopelessness and frustration in the couple.
When a couple fails to achieve a pregnancy after undergoing several cycles of IVF treatment in Delhi using three healthy embryos, they are said to be going through repeated IVF failure or recurrent implantation failure.
Causes of Repeated IVF Failures:
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Poor quality of oocytes
A healthy egg or oocyte gives rise to a healthy embryo upon fertilization. The egg fuses with the sperm to form the embryo and any abnormalities in the egg may result in a chromosomal abnormality in the embryo. Often during cell division during formation and or maturation of the oocyte, there may be some errors in replication such as non-disjunction, thus leading to abnormal segregation of the chromosomes. This may lead to the most common kind of chromosomal anomalies – aneuploidies (trisomies or monosomies). Such chromosomal abnormalities such as deletions, duplications or aneuploidies lead to the embryo being rejected for implantation thus resulting in IVF failure.
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Poor quality of the sperm
Abnormalities in the sperm may lead to the egg remaining unfertilized. The sperm has three major roles to play in fertilization:
- To travel towards the egg through the fallopian tube,
- the outer membrane of the egg penetration
- To fertilize the egg by releasing the haploid genetic material or the DNA to produce an embryo.
It is thus crucial to select the best quality sperm under high magnification during an IVF procedure for successful fertilization. Sometimes a high-quality sperm though may have normal chromosomes but may lack the enzymes required to dissolve and penetrate the zona pellucida which is the outer shell of the egg. Sperms of low quality, morphologically abnormal and low motility may not be able to reach the egg to fertilize it.
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Unhealthy Embryo
The selection of a healthy embryo plays a crucial role in the outcome of the IVF procedure. Often, an embryo with a genetic abnormality either at the DNA or chromosomal level is spontaneously rejected by the uterus. The uterus is programmed to accept a healthy embryo and any abnormality would lead to an implantation failure or miscarriage. Though it is difficult to differentiate the morphologically normal embryos from the abnormal ones, there are certain genetic tests that can be recommended to diagnose such abnormalities and further test the embryos to ensure they are healthy. Such genetic testing in the embryos is known as Pre-implantation genetic testing.
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Uterine Problems
The endometrial environment is crucial for the success of an implantation post an IVF procedure. There are different types of structural, hormonal and immunological factors that affect the uterine environment.
Structural uterine factors that may cause repeated IVF failures are:
- Abnormal shape of the uterus
- Presence of fibroids and polyps
- Uterine scarring
- Hostile cervical environment
- Intrauterine adhesions
Other abnormalities associated with the uterus include the formation of a thin endometrial lining due to an early rise in the progesterone prior to the egg retrieval in an IVF cycle.
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Maternal and Paternal Health
The health of the couple or to-be-parents is a very important factor that determines the success of the IVF procedure. Lifestyle habits like smoking, consumption of alcohol and recreational drugs could lead to complications during the pregnancy and thus result in miscarriages or implantation failures. Chronic health conditions such as diabetes and hypertension, if left unchecked could also cause repeated IVF failures in the couples undergoing the procedures. Certain autoimmune conditions also cause the mother’s body to reject the embryo thus leading to implantation or spontaneous miscarriages. It is important to get evaluated by a specialist in case of any such conditions.
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Issues with Embryo Transfer
The transfer of an embryo post-fertilization is a non-surgical procedure and is very sensitive. AN alteration or error in the procedure may lead to an implantation failure. It is crucial that the embryo be transferred to the ideal location in the uterus which can be ascertained by doing a trial transfer prior to the actual embryo transfer.
Diagnostic tests to identify the cause of Implantation Failure: –
There are several tests that can be recommended by doctors to determine the cause of Implantation failure of an embryo:
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Uterine Evaluation using as Hysterosalpingogram (HSG)
It is important to evaluate the uterine cavity for any structural anomalies prior to the IVF procedure. The Hysterosalpingogram test is a specialised test that can evaluate both the uterine cavity and the fallopian tubes to check their integrity and for the presence of any blockages. A hydrosalpinx (blocked fallopian tube due to a fluid-filled cavity) reduces the chances of implantation by almost 50%.
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Sperm DNA Fragmentation Test
This test is important as it evaluates the integrity of the DNA carried by the sperm. Any breakage or fragmentation in the sperm DNA is known to cause lower fertilization rates, implantation failure and spontaneous miscarriages.
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Endometrial Receptivity Assay (ERA)
The success of embryo implantation largely depends upon the window of implantation of the endometrial lining. The endometrial lining is the tissue in the uterus which accepts the embryo for implantation. Often the window of implantation gets displaced within a particular uterine cycle and thus implantation fails to take place. The Endometrial Receptivity Assay (ERA) is a specialised genomics test that looks at the gene expression of the endometrial tissue to predict the exact time for implantation. A small biopsy tissue of the endometrium is taken (during a non-treatment cycle) and the ERA test is done to determine the window of implantation for the upcoming treatment cycle. This helps increase the chances of implantation of the embryo when transferred.
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Pre-Implantation Genetic Testing
Often genetic abnormalities in the embryo lead to the failure of implantation or spontaneous miscarriage of a pregnancy during the early weeks. This can be overcome by Pre-Implantation Genetic Testing for Aneuploidies (PGT-A). When the number of chromosomes in the embryo is more or less than the normal complement, these are known as aneuploidies. The PGT-A test helps to determine which embryo is healthy and free from chromosomal anomalies. Those can then be taken ahead for transfer.
