Prof. Oladapo Ashiru

By Oladapo Ashiru
In this New Year, a good number of couples have as their focus the need to have a baby or add one to their family. While it is easy for some people, global statistics indicate that up to 75 percent of those attempting to have babies are not able to do so.

Even as new technologies such as In vitro fertilisation and embryo transfer are being developed to assist these groups, a high percentage who use such technology do not conceive easily. A good number will attempt IVF two or three times and would not get pregnant. The condition is referred to as recurrent implantation failure. I have chosen to write on this subject with a view to giving some insight to those who may have the need.

Recurrent implantation failure is the inability to achieve a clinical pregnancy after the transfer of four good quality embryos in a minimum of three fresh/frozen cycles in a woman under the age of 40.

Recurrent implantation failure is an essential cause of repeated IVF failure. It is estimated that approximately 10 per cent of women seeking IVF treatment will experience this particular problem. It is distressing to patients, frustrating to the doctors and increases the overall cost of the procedure.

Categories of people prone to RIF

Older women, overweight, longer infertility duration, a higher hormone level, and needed more gonadotropin doses in controlled ovarian hyperstimulation and partners with sperm motility and morphology

RIF could be a result of the embryo, uterine factors or other multifactorial factors.

The embryo is made up of the egg and the sperm. In the clinical practice of human in vitro fertilisation, pregnancy is dependent on embryo implantation. Pregnancy is a function of the number of embryos transferred, with multiple embryos resulting in a higher likelihood of pregnancy. Nowadays, single /double embryo transfer is preferable.

Embryo implantation is dependent on transfer efficiency, embryo quality, and endometrial receptivity.

When it comes to embryo transfer, more is not necessarily better; better is better. In other words, quality is more important than quantity.

Reasons for poor quality embryo

Sperm quality
When a couple ends a cycle with poor quality embryos, the focus is usually on the eggs. But now there is more focus on sperm quality as a cause of poor embryo quality, specifically the degree of DNA fragmentation in the sperm. DNA fragmentation of morphologically normal sperm negatively impacts embryo quality and the probability of pregnancy in ICSI cycles.

Egg quality
It is dependent on the age of the woman, the ovarian reserve (the number of follicles counted at baseline on ultrasound), the hormonal level in the first few days of menses. A woman is born with all the eggs she will ever have.

After the menarche (age at which menstruation starts), a monthly process of repeatedly processing eggs continues until the menopause, by which time most eggs will have been used up, and ovulation and menstruation cease.

It is mostly the egg, rather than the sperm that determines the chromosomal integrity of the embryo and only a fetus that has a standard component of 46 chromosomes, euploid is “competent” to develop into a healthy baby.

If for any reason the final number of chromosomes in the egg is less or more than 23, it will be incapable of propagating a euploid, “competent” embryo. Thus, egg/embryo aneuploidy is the leading cause of human reproductive dysfunction which can manifest as arrested embryo development and failed implantation.

The incidence of embryo aneuploidy invariably increases with advancing age. Consequently, infertility, miscarriages and congenital disabilities double as women get older.

Exposure to environmental toxins, radiation, systemic and pelvic pathology or surgery that compromises ovarian blood flow, can affect the egg quality in women.

Uterine factors
Uterine factors associated with some implantation failures in the setting of infertility, recurrent loss and IVF can occure, such as mechanical, inflammatory and systemic factors.

Mechanical factors:

Congenital uterine anomalies and acquired intrauterine conditions.
Acquired intrauterine conditions such as submucous fibroids, endometrial polyps, and intra-uterine adhesions depending on size and location have also been linked to poor obstetric outcomes and may also contribute to recurrent implantation failure.

Inflammatory factors associated with implantation failure include endometriosis, adenomyosis, hydrosalpinges or a blocked fallopian tube and endometritis, inflammation of the endometrium.

Systemic factors

Polycystic ovary syndrome, a common cause of infertility affecting reproductive-aged women, is associated with reduced endometrial receptivity. Progesterone resistance, which is associated with inflammatory changes in the endometrium, has been observed in both endometriosis and PCOS.

Multifactorial factors that can affect embryo implantation include:

Thyroid function
Thyroid hormones influence the feto-maternal interface through interactions with thyroid hormone receptors and thyroid stimulating hormone receptors present in the endometrium and trophoblast during implantation. Abnormalities in thyroid function can hurt reproductive health and result in reduced rates of conception, increased miscarriage risk and adverse pregnancy and neonatal outcomes

Prolactin
Circulating levels of prolactin hormone is elevated during ovarian stimulation cycles in some women which can ultimately affect ovarian response and pregnancy outcome.

Lifestyle

Obesity
It is a common and treatable cause of poor pregnancy rate following IVF.

About 35 per cent of reproductive age women are obese (body mass index [BMI] ≥ 30 kg/m2). These women are more likely to be infertile and have poor pregnancy outcomes.

Cigarette Smoking
Cigarette smoking is a modifiable factor that impacts reproductive success. It causes reduced blood flow to the endometrium and thereby hindering implantation.

Management of Recurrent Implantation failure

To improve IVF outcomes, the focus is on two areas:

Assessment of embryonic competence and
The optimization of endometrial receptivity.

Couples who have experienced one or more failed IVF cycles are invited for a consult with the attending physician after a thorough analysis of their case (file). The outcome of the investigation is discussed with them, and any factor(s) identified would be managed accordingly.

Sperm DNA fragmentation — lifestyle changes, exercise, and weight loss, vitamins supplementations, shorter intervals of ejaculation before the IVF specimen and in rare cases, obtaining sperm by testicular biopsy.

The Female Patients;
Lifestyle changes such as exercise to combat obesity, stop cigarette smoking, zero or low alcohol intake.
Ovarian improvement drugs may also be recommended to improve the egg quality. Early age of starting treatment is also advocated for women, and donor eggs counseled where necessary.

Pregnancy outcome has improved significantly with the use of surgery in correcting intrauterine pathologies like fibroids, polyps, intrauterine adhesions, and septate uterus (divided by a membrane) has shown a significant increase in pregnancy outcome.

Supplement drugs given for low thyroid levels elevated prolactin levels would be managed with a dopamine agonist and luteal phase support where deficient.

Overall, couples are counseled to try again, because subsequent embryo transfers have been associated with significantly higher pregnancy rates.

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