January 22, 2021 4:46:24 pm
By Dr Santosh Gupta
With a growing infertility problem, IVF today has become a well-known and widely accepted technology that is safe, efficient and reproducible. IVF has come a long way from 1978, with the birth of the first IVF baby, which can be attributed to improved drugs, better lab equipment and an evolved culture and media. IVF in today’s scenario has reached the success rate exceeding 50 percent, showing constant growth and improvement in terms of achieving success.
As technology cannot promise guaranteed success, some couples seeking IVF treatment might face failure in spite of doing multiple cycles, which we label as recurrent implantation failure. It can be very emotionally and financially draining, where in spite of trying hard, a couple fails to achieve pregnancy. RIF is technically defined as when four or more good quality embryos are transferred or three failed transfers with good quality embryos.
Failure of embryo implantation can be because of embryonic factors, oocyte or sperm or uterine factors. Advanced maternal age is one of the common reasons as late marriage and delay in planning pregnancy has become very common. Obesity, smoking, stress and poor lifestyle are other contributing factors.
Advance semen analysis and DFI, test for endometrial receptivity and genetic analysis of embryos before transfer can throw some light on causes of RIF.
Detailed pelvic scan of the female partner, if required, 3D pelvic scan to rule out uterine malformations, intrauterine adhesions, and small submucous fibroid or endometrial polyps. Even presence of hydrosalpinx could be the cause of implantation failure. Some patients have adenomyosis which can be well appreciated in a scan and such patients are given different medical therapy to increase the chances of implantation; large intramural fibroids if present should be removed in RIF cases.
Hysteroscopy is another important tool to diagnose and treat RIF cases. The presence of septum or adhesions in the uterus can be corrected during hysteroscopy. Chronic infection of the endometrium is one of the causes, which can be identified with hysteroscopy and biopsy, which can be treated with specific antibiotic therapy. Laparoscopic disconnection of fallopian tubes will help if a hydrosalpinx is present.
IMPROVING EMBRYO SELECTION
In the initial years of IVF, embryo transfer was done on day 2 or day 3 of embryo development. As technology improves, we are able to culture embryos till day 5 or day 6 to form a blastocyst stage embryo.
Normally, an embryo comes to the uterus at the blastocyst stage. The implantation rate of blastocyst stage embryo is higher than cleavage stage as it improves the selection process. The use of morphokinetics to select the best embryo will further add to the success rate. Preimplantation genetic screening (PGS) of embryos will provide further information whether embryos are genetically normal or not.
Patients with RIF develop a high percentage of chromosomally abnormal embryos which will not implant in spite of morphologically looking good. Usually, embryos are cultured till blastocyst stage and then a biopsy is done to check the chromosomal makeup of embryos. If the report comes normal, i.e. euploid, then those embryos are chosen for transfer. Euploid embryos have a higher implantation rate and very high success rate.
ASSESSMENT OF ENDOMETRIAL RECEPTIVITY
Normal transvaginal scan assesses the thickness and pattern of endometrium and, if it is trilaminar and 8mm or more, it is good for implantation. Blood flow to the endometrial can be assessed by Doppler studies blood up to zone 3 is associated with good implantation rate. The concept of implantation window is very well known. In some cases of RIF implantation window is disturbed and we have to shift the timing of embryo transfer as per report, a process known as personalised embryo transfer. This can be assessed by a test called endometrial receptivity assay (ERA) which will tell us whether endometrium is receptive, post-receptive or pre-receptive and accordingly, we have to plan embryo transfer for the patient.
ERA test will provide us information for personalised embryo transfer.
There is some evidence that endometrial scratching will increase implantation rate although large trials fail to, so any improvement in success but clinics use intravenous immunoglobins or interleukins. Another controversial treatment is use of autologous platelet rich plasma (PRP).
Sometimes, autoimmune diseases like SLE and abnormal coagulation profile could be the cause of implantation failure. Blood work to detect and treat them medically before the next embryo transfer is recommended. In these scenarios, aspirin and low molecular weight heparin has a role to play. In case of immune disorder, immunomodulatory drugs are recommended.
Changing stimulation protocol to get better number and quality of oocytes might work in few patients. If all transfers were fresh then choosing a frozen embryo might work better as the endometrium is more receptive in the frozen embryo cycle in comparison to stimulated.
RIF is a very frustrating situation both for patients and clinicians. A personalised approach for subsequent treatments is key to success.
(The writer is Fertility Consultant, Nova IVF Bengaluru)
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