There is a fair amount of timing that goes into optimizing the implantation of a fertilized egg. Also known as a “Blastocyst” it only has a narrow window of sometimes only two days to successfully implant in a fertile endometrial lining.

There are a series of master regulators that need to be carefully synchronized with other things like estradiol and progesterone receptors. Also known as PR-A and PR-B they are expressed by the epithelial and stromal compartment of the human endometrium. Other factors that might be involved also include PR-A and PR-B signaling during implantation. These intricate functions tend to be executed by things like juxtacrine, paracrine and autocrine factors. Each of these work in concert with various growth factors, cytokines, lipid mediators, and homeobox transcription factors as well as morphogens.

For fertility specialists and couples who are hoping to conceive via IVF treatments understanding the intricacies of this so-called “Molecular Clock” can make all the difference between the absence or presence of an embryo. The goal then turns toward understanding how these endometrial receptivity factors interplay, in a narrow window of time, which can often span only two short days!

Personalized Diagnostics Can Significantly Improve Embryo Implantation Rates

A personalized strategy is often called for to improve overall embryo implantation rates. This starts with a series of highly accurate, yet personally customized diagnostics. Things like CD56 bright uterine NK cells which are also typically implicated in the control of the invasion phase as well as the vascular remodeling of the placental bed are not always fully understood.

Sometimes a pattern of Recurrent Implantation Failure or “RIF” is also characterized with seemingly major alteration in key hormone interaction in a uterine “Molecular Clock. This, in turn, can potentially prevent the final success of an assisted reproductive treatment.

At the same time, you should also bear in mind that a Recurrent Implantation Failure pattern is technically defined as at least three or more failed IVF cycles. Each of which was known to produce one or two morphologically high-grade embryos which were either transferred or could have been transferred to the uterine lining.

These clinical situations and the personal emotions experienced by the parents often leads to a higher patient drop-out rate. When all along there may have been a molecular clock or hormonal factors at play that had no direct bearing on the couple’s ability to produce a viable embryo.

This seeming disconnect between the interaction of IVF with successful fertilization and the synchronicity of the uterine lining can point to other underlying factors which need to be addressed. This could include pathological alterations such as:

  • Hyperplasia
  • Submucous myomas
  • Submucosal polyps
  • Endometritis
  • Hydrosalpinx
  • Synechiae

In cases where these conditions might be a factor, further diagnostics will likely be needed. With a condition like Synechiae, an estimated 18 to 27% of cases have some level or increased incidence of embryonic chromosomal abnormalities. Anyone of which could be linked to lifestyle factors or could be hereditary as well as a possible acquired thrombophilia.

Treatment Or Correction Of Pathological Issues May Be Only The First Step Toward Successful Implantation

In the case of some pathological conditions that affect uterine health or receptivity, there may be effective treatment options. Your physician and fertility specialists can help you understand the treatment strategy that is right for your situation. Some of these conditions might not have a 100% treatment or cure rate. However, there might still be things that can be done to reduce symptoms or otherwise increase the chances of uterine receptivity.

Yet even in a percentage of cases, where treatment strategies improved pathological symptoms, successful implantation might still be hampered by other factors. A growing body of research strongly suggests that successful implantation of an embryo requires synchrony between both the embryo and the intended endometrium. While there are no hard and fast conclusions at this time, an infertility workup is necessary for all women who have been classified as a RIF patient.

A Case Study Sheds Light On The Process

A study conducted in 2008, reported the case of a then 39-year old woman who had experienced two previous IVF failures. In each of these cases, the embryos were fully viable, yet they failed to implant in the uterine lining through traditional methods.

Extensive diagnostics were performed, which revealed a sub-septate uterus. In this instance, surgical correction was possible and with the help of her physicians, she was able to achieve normal uterine morphology.

After extensive counseling, the couple underwent an additional two IVF treatment cycles. Each of these produced viable embryos suitable for transfer. The first was a “Fresh” or active cycle, and then another which was a “Frozen” cycle. Yet neither one proved to be successful.

At that point, the couple turned to donated oocytes, and sperm from the recipient’s partner, which were used to create embryos suitable for transfer. The first attempt used a pair of “Day-Three” embryos which were transferred as part of a Hormone Replacement Therapy cycle. This was followed by 2 days of progesterone replacement. Unfortunately, this effort also failed to implant successfully in the uterine lining.

The couple’s next attempt was performed by transferring a pair of good quality “Day-Three” embryos as part of a natural cycle This was also three days after natural ovulation had been triggered by administering hCG. However, this too was also unsuccessful. At that point, a third oocyte donation cycle was performed which used two high quality “Day-Five” blastocysts which were transferred in an HRT cycle after 5 full days of progesterone therapy. Yet again the embryos failed to implant in the uterine lining.

At that point, an endometrial biopsy was collected during the Day-Five HRT cycle, which was identical to the previously failed embryo transfer. This diagnostic test revealed that her endometrium was pre-receptive.

A further Hormone Replacement Therapy cycle after seven days of progesterone replacement achieved a receptive endometrium which was indeed appropriate. At that point, two blastocysts were performed in her next cycle which resulted in a successful twin pregnancy. The gestational cycle was perfectly normal and healthy. At 36 weeks the woman delivered two healthy boys by Cesarean section.

Her willingness to endure repeated implantation failures, to find the underlying cause, proved to bear exactly the fruit she had set out for. Truly a case of how modern-day diagnostics and persistence can pay off in the end!

Source – OUP