What If The IVF Treatment Fails? What Are Your Options?

Negative pregnancy test

What If The IVF Treatment Fails? What Are Your Options?

A failed IVF cycle is devastating emotionally, physically and also financially. Unfortunately, this is the reality for up to 30% of patients who are unable to conceive for an unknown reason.
In some of these cases, the embryo fails to implant in the endometrial lining. The embryo then disintegrates and expelled when the endometrial lining is shed. Women may experience a slightly heavier period flow.
However, it becomes apparent that some women experience substantial more implantation failures than others and so the term Recurrent Implantation Failure, or RIF was coined.

What is RIF?

Although very difficult to clinically define RIF, the current consensus definition is when ten embryos or more have been transferred with no recorded implantation.

So why some embryos fail to implant? What are the reasons?

Let’s use the analogy of sprouting seeds to explain this. For a germination to occur it will need specific conditions: High-quality seeds, soil and environmental conditions (clean water, etc.) In the same way, there can be three logical reasons for implantation failure:

Poor quality embryo (the seed) – Embryos with genetic abnormalities

The Uterus (the soil) – The uterus lining (endometrium) is not “ready” for implantation

Physical health of the mother (the environment)

All those factors are equally important for implantation to occur. In this blog post, we will examine the endometrium as one of the reasons for RIF.

The Endometrium is the mucous membrane lining the uterus, which thickens during the menstrual cycle in preparation for possible implantation of an embryo. Human uterus is receptive for implementation for a short period between 2 to 4 days post ovulation. This period is also called as the period of “uterine receptivity” or “implantation window”. On average, it occurs during the 20th to the 23rd day from the first day of the last menstrual period. During IVF, in current practice, most embryos are transferred to the uterus on day 5-6(blastocyst transfer) after egg collection (the day of ovulation) which coincides with the beginning of“window of implantation” of a natural menstrual cycle. However, research shows that, due to a uniquely different rate of endometrial development, 20-25 percent of embryo transfers occur on the wrong day (either too early or too late) which explains the implantation failure.

What can be done improve Endometrial receptivity?

The first step is to determine accurately when is the implantation window. This can be achieved by:

  • Endometrial Histological analysis – Histological analysis of an endometrial biopsy can date the endometrium and diagnose “out of phase endometrium” or “OOP endometrium”.
  • Endometrial Receptivity Array (ERA) – a novel diagnostic test that evaluates the level of implementation receptivity by molecular analysis of the endometrial tissue. The biopsy of the endometrial tissue is analyzed for the expression of 238 genes involved in implementation. The ERA results allow doctors to identify the exact time when the endometrium is most receptive and by that to select the optimal time for embryo transfer for increased chances of implantation and pregnancy.

Both methods are available to Juno’s patients and are part of the tools Dr. Bentov uses to personalize a treatment plan to our patients. The need of each method is decided upon complete evaluation of patient medical history and other test results. Both methods will require endometrial biopsy which is a minimally invasive procedure where a catheter-like device is inserted through the cervix into the uterine cavity to obtain a tissue sample. The test only takes few minutes to perform. The ERA test is a more expensive test but is found to be more accurate in determining the implantation window.

Once the receptivity window is defined what else can be done to improve implantation?
The below therapies can be used to increase receptivity. However, it is important to note that more clinical evidence is needed to determine their efficacy:

1. Endometrial scratching –

Local endometrial injury by biopsy or hysteroscopic resection before IVF cycle could promote endometrial receptivity and implantation. It was shown to synchronize endometrial maturation and increase the secretion of inflammatory cells which are needed for successful implantation. However, more large-scale studies are needed to confirm this finding. This is phenomenon is achieved as a byproduct of sampling the endometrium for detecting the window of implantation.

2. Use of Aspirin –

Aspirin is an inexpensive drug that promotes dilation of blood vessels and may improve blood flow to the uterus. It was proposed to enhance implementation and pregnancy rates when given as a treatment during IVF. The use aspirin during IVF is still controversial, and debate is ongoing.

3. Use of Heparin –

Heparin is a blood thinner. Heparin prevents the formation of blood clots and may improve attachment of the embryo to the endometrium.

4. Use of Steroids, IVIG or Intralipids –

These therapies are used to reduce the level of specific immune cells called NK cells in the uterus. This immune alteration is favorable to support a pregnancy.

5. Use of G-CSF –

(Granulocyte-Colony Stimulating Factor), a cytokine which stimulates the proliferation of specific immune cells which can help improve the outcomes in patients with recurrent miscarriages.

6. HCG infusion –

HCG is a glycoprotein that is initially secreted by the early developing embryos. HCG activity improves endometrial adhesion, development of blood vessels (angiogenesis). Intrauterine infusion of natural or recombinant HCG before embryo transfer showed to increased implementation and pregnancy rates.

Based on the test results the fertility specialist will suggest a personalized treatment plan to optimize the chances for implantation. At Juno, we strongly believe in patient-centered care. Informed patients who understand their options and are engaged in the decision-making process are an integral part of successful treatment.

In the next blog, we will discuss the embryo and how it plays a role in the implantation process and what can be done to improve the chances of successful implantation and pregnancy rate. Stay tuned!

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