Unfortunately, some women suffer from repeated IVF failure, which causes lot of distress to the couple. However, there are no clear answers till today.
What is Recurrent Implantation Failure?
- VFailure to achieve clinical pregnancy after transfer of four good quality embryos in a minimum of three fresh or frozen cycles in a woman under the age of 40 years is known as Recurrent Implantation Failure.
- It occurs in 10% of women undergoing IVF due to various causes. Implantation is the key event in the establishment of pregnancy.
- Successful implantation requires interaction between embryo and endometrium.
- The failure to implant may be secondary to either fault in embryo or endometrium. In two third of cases embryo is at fault and in one third of cases endometrium is at fault.
One needs to be sure about the ovarian stimulation protocols, endometrial thickness and blood flows, no technical difficulty encountered during the embryo transfer and about the laboratory quality control before we label it as Recurrent Implantation Failure. Patient characteristics like oocyte quality and maternal age play key role in determining outcome.
What are the causes of Recurrent Implantation Failure?
The causes of RIF are diverse and may be due to:
- Anatomic factors such as uterine pathology such as endometriosis, endometrial polyp, fibroid, adhesions, hydro salpinges.
- Male factor may also contribute to the morphology of the embryo, when severe oligoastheno teratospermia or increased DNA fragmentation is there.
- Morphology and genetics of embryo where morphology of embryo may be good but it has aneuploidy or there may be poor quality Oocyte / Sperm / Embryo / Zona Hardening.
- Hormonal or metabolic disorder (uncontrolled diabetes, thyroid disease, high prolactin levels)
- Infections of the genital tract
- Thrombophilia or Antiphospolipid syndrome – Small clot in the blood may be a cause for recurrent implantation failure
- Immunological factors
- Psychological factors, lifestyle
- Endometrium RIF – Chances of failure of Implantation are high if endometrium is 6 mm However if no cause is identified, we label it as Idiopathic RIF – (Impaired cross talk between embryo and endometrium) which is defined as unexplained failure with transfer of good quality embryos in a normal uterus with thick endometrium.
How are these couples evaluated?
We offer comprehensive investigations in these couples:
- Ovarian assessment is done by AMH, Antral Follicular Count, Day 2 S.FSH levels.
- Thrombophilia screen – In some individuals blood clots more easily than normal and may be a cause for recurrent implantation failure. Lupus anticoagulant and Anticardiolipin antibodies are the two most commonly test performed to rule out thrombophilia disorder.
- Immune screen – To assess increase levels of natural killer cells and autoantibodies. More studies are needed to warrant the routine use of steroids, IVIG and intra lipids to suppress the immune system.
- Endometrial Tests – 3D Ultrasound to ensure there is no anatomical or structural variation like fibroid, polyp, hydrosalpinx, endometrium.
- Sperm DNA Fragmentation Test – Assessing degree of damage to sperms by this technique helps in identifying those couples who would be benefitted by ICSI.
What are the treatment Options for these couples?
Counselling is an integral part of evaluation of a patient of recurrent Implantation Failure. We have special failure counselling session for these patients in coordination with embryologist, psychologist, Ultrasonologist where critical analysis is done in detail right from stimulation protocol, Embryology details in terms of right from oocytes retrieval to number of oocytes fertilized to number of embryos transferred, if any difficulty encountered during embryo transfer.
We offer advanced treatment options and support for these patients. Treatment is aimed at improving embryo quality or endometrial receptivity. To improve endometrial receptivity, the following approaches may work in individual cases depending upon the case.
- Hysteroscopy – is of proven benefit in recurrent Implantation Failure. Correction of undiagnosed scarring, polyps or synachiae on hysteroscopy improves pregnancy outcome in RIF.
- Endometrial Scratch – might improve implantation rate in some cases. The lining of the uterus (endometrium) is gently scratched using a fine, flexible plastic catheter which is passed through the cervix.
- Scratching the endometrium releases certain growth factors, hormones and alteration in gene expression which makes the endometrium more receptive for implanting embryo and thus increases the chances for successful pregnancy. It is an OPD procedure done without anesthesia on day 21 of the previous cycle of planned IVF. More research is underway to understand exactly how this works.
- Endometrial Receptive Array – Sampling Endometrium and analysing for the presence of over 248 genes associated with implantation may give answer in few patients.
- Hydrosalpinges – Salpingectomy or clipping of fallopian tubes by laparoscopy prior to IVF in proven case of hydrosalpinges improves pregnancy implantation, and live birth rate.
- Paternal Factors ICSI – ICSI is beneficial for those who show increased degree of damage to sperms by Sperm DNA Fragmentation Test.
- EMBRYONIC Factors– Blastocyst culture, assisted hatching, Coculture of embryo with endometrium, Donor Oocyte / Embryo may give answer in few patients. Advanced technologies like PGS/PGD may give help in some patients. Embryoscope – Time Lapse Recording allows us to assess subtle changes during embryo development and identify the best embryo for transfer
- Reproductive Immunology– There is no benefit use of giving steroids, IVIG and heparin and low dose aspirin. Our comprehensive and meticulous approach has brought smiles to patients with recurrent implantation failure.