Implantation Failure

 

Multifactorial factors

Multifactorial effectors :

  • Endometriosis
  • Hydrosalpinges
  • Suboptimal ovarian stimulation

Multifactorial causes :

  1. Endoemtriosis leads to implantation failure
  2. All markers of reproductive process, including ovarian response, embryo quality, implantation and Pregnancy rates are decreased in endometriosis and the decrease is directly proportional

Hydrosalpinges :

Have lower implantation and Pregnancy rates.
Hydrosalpinx fluid is commonly slightly alkaline and may contain cytokines, prostaglandins or other inflammatory compounds .

  • These compounds may have either direct embryo toxicity or adersely affect the endometrium.
  • Reflux of hydrosalpinx fluid into the uterine cavity may result in diminishing embryonic endometrial apposition
  • Endometrial and embryo qualities may be harmed by certain drugs→ given for ovarian stimulation

Multifactorial treatment options :

  • Treating endometriosis
  • Danazol
  • Salpingectomy in case of hydrosalpinges
  • Tailoring the stimulation protocols
  • Psychological assistance.

Multifactorial treatment options :

Treating endometriosis :

  1. Administration of GnRH agonists for 3-6 months before ART in women with endometriosis significantly increases the ongoing pregnancy rates.
  2. No deleterious effect on ovarian response was observed
  3. Clinical pregnancy increased 4- fold with this treatment
  4. Role of laparoscopic treatment of non-ovarian endometriosis in patients with failed IVF is controversial.
  5. Surgery might prove deleterious for ovarian reserve.

Danazol :

  1. Immune suppressive effects of danazol are beneficial in suppression of endometriosis
  2. Pregnancy rates significantly increase with this treatment
  3. Danazol increases the endometrial receptivity and upgrades the endometrial α V β 3 integrin.

Salpingectomy of Hydrosalpinges :

  1. Laparoscopic salpingectomy is recommended for women with hydrosalpinx before IVF treatment in implantation failure group.
  2. Salpingectomy in hydrosalpinx women increases pregnancy rates.

Tailoring the stimulation protocols :

GnRH-antagonist protocols improved blastocyst quality and pregnancy out come after implantation failure with GnRH-agonist protocols
Natural cycle is also suggested. Particularly in patients with high uterine NK cell count
Changing any specific medication or stimulation protocol can improve treatment outcome.
Certain patients are more vulnerable than others to certain medications, thus, there might be a place for ‘personal’ protocol in implantation failure

Psychological assistance :

  1. Stress can interfere with infertility treatments
  2. Psychotherapy [individual or group] reduces anxiety and depression and possibly enhances conception success.
  3. We recommend psychological interventions and various relaxation techniques, but proof of their efficacy is lacking.

Personal experience :

  • There are many reasons for implantation failure
  • We believe that we do not have the tools to diagnose in each and every case the exact cause for the repeated failure. After failure of three transfers of good quality embryos in a unit with a PR of atleast 30% one should take some special measures .
  • Each individual case should be analyzed specially to see the reason and the treatment tailored according to the needs to enhance the pregnancy outcome.
  • Everyone agrees that taking a different approach achieves a pregnancy in many cases that failed repeatedly.
  • After three failures repeated hysteroscopy and atry of blastocyst transfer are highly recommended
  • Change in the stimulaton protocol has a place
  • AH, PGS and co-culture are probably beneficial in experienced hands.
  • Long –term use of danazol or GnRH agonists probably has a place in repeated failures with endometriosis
  • Frozen embryo transfer can also be considered
  • Use of IVIG is controversial but may be justified after many failures in specific cases
  • Steroids might have place in patients with any sign of autoimmunity, and ZIFT has a place in cases of difficult embryo transfers.