REPEATED IVF/ IMPLANTATION FAILURE (RIF) PART 2

Repeated Implantation Failure(RIF) as discussed last week is an important cause of repeated IVF failure. It is a distressing condition for patients and very challenging one for clinicians, it is therefore essential to understand underlying factors and possible management. This week, we will be concluding with the Embryonic factors affecting pregnancy and male contribution to RIF.

The Endometrium: The endometrium is the inner lining of the womb where embryos implant hence a functioning and receptive endometrium is crucial for embryo implantation. During the menstrual cycle, the endometrium undergoes both morphologic and biologic changes that prepares it for interaction with the embryo, and ultimately for successful implantation. Once all biological changes transpire, the embryos can attach, invade the endometrium and finally implant.

The crucial stage last for a few days and is referred to as the ‘’ the window of implantation’’. In this stage, the endometrium must proliferate, increase in thickness and then after ovulation, adequately respond to progesterone and become receptive. Ultrasound examination of the thickness and appearance of the endometrium is an easily performed means of assessing morphological changes occurring in the endometrium during the follicular phase, and thus used as a measure to predict successful implantation. Indeed, several studies have reported a strong association between endometrial thickness and successful implantation. Implantation has been achieved in women with endometrial thickness of 6-8mm. Thin and unresponsive endometrium may result following previous surgical intervention within the uterine cavity.

Management of thin endometrium has been achieved using high dose Estradiol or vaginal Estradiol, this is meant to increase the blood level of Estradiol. Other medications include the use of Aspirin and sildenafil tablet intended to increase blood flow to the endometrium.

Embryonic Factors.

The second player in the equation of successful implantation is the embryo. Implantation is in fact not an efficient process, as the natural conception rate within timed intercourse in otherwise healthy young couples is only about 25%. Inadequate receptivity, as discussed earlier is responsible for approximately two-thirds of implantation failures, whereas the embryos itself is responsible for only one-third of these failures. These Embryonic factors may include:

Abnormal Karyotype: Abnormal karyotype of the embryos is one of the major reasons for failure in implantation and miscarriage. Both male and female partner may produce aneuploidy (abnormal chromosome) gametes, thus two-third of the generated embryos may be abnormal, fail to implant or be aborted after implanting. Couple with RIF should be encouraged to do a karyotype (test done to look at the number and appearance of chromosomes in the nucleus of the cell). Couple found with abnormalities should be offered preimplantation Genetic Testing (PGT).

Zona Pellucida: The zona pellucida is the outer wall/covering of the female egg, the fertilized egg undergoes growth and development until it gets to the blastocyst level where it is ready to hatch through the zona pellucida. This is an essential step preceding implantation. Hatching involves both chemical and mechanical processes which eventually lead to the thinning of the zona pellucida as well as its rupture and blastocyst hatching. Abnormalities of the hatching process may contribute to failed implantation in an IVF attempt. The laser assisted hatching may be clinically useful in women above 38 years with RIF.

Embryo Culture and Transfer: The definition of RIF refers to the transfer of good quality embryos that do not result in implantation. Embryo quality is assessed by morphological criteria, under the assumption that the embryo although transferred on either day 2 or 3 after fertilization, would continue to develop in uterus and fail to progress into blastocyst stage. This may be due to either suboptimal local condition or intrinsic factors. Several approaches have been suggested for overcoming these obstacle, and they include Zygote Intra Fallopian Transfer (ZIFT) which is the process of transferring the day 2-3 embryos directly to the fallopian tube where it continues development. This process is more related to the natural development of embryos in the body and has been found to be very effective in improving the success rate of IVF among women with RIF.

Blastocyst Transfer: A blastocyst is an embryo that has been cultured to develop in the incubator for at least 5 days. The success rate of blastocyst transfer is higher than day 2-3 embryo transfer. Culturing embryos to blastocyst stage will serve two goals. First of all, it enables better selection of embryos for transfer, secondly blastocyst is the normal stage embryos get to before implanting within the endometrium, hence we actually mimic nature when we transfer a blastocyst into the endometrium rather than a day2-3. The chance of achieving the ‘’window of implantation’’ is high too. Hence in women with RIF the transfer of blastocyst has been of immense benefit as it has been proven to have better implantation rate as well as live birth.

Male Contribution to Embryo Competence for Implantation

Several researches have been proven that low sperm quality can decrease the success of IVF due to abnormalities in the sperm and DNA fragmentation. Researchers also report that the performance of sperm cells with poor morphology is low and also associated with high level of DNA fragmentation. This results in poor fertilization and implantation rate.

The use of IMSI (Intracytoplasmic morphologically selected sperm injection) can help to detect DNA fragmentation. IMSI selected sperm cells have been associated with high implantation and live birth rate.

Conclusion

The dilemma of repeated implantation failure can be overwhelming; it is important to talk to your fertility specialist so that together you can overcome this challenge