Infertility & Causes
The successful implantation of an embryo and its healthy development into the uterus are directly dependent on the normal functioning of the following processes:
A well regulated hormonal interaction system coordinating normal ovulatory cycles, releasing genetically and structurally healthy eggs which can become fertilized by healthy spermatozoa within patent fallopian tubes and develop into early embryos that can be conceived in a uterus of optimal size and contour.
Any inherited or acquired condition which can compromise the normal processing of these mechanisms will subject a female sub-fertile or infertile.
When a female child is born and unless she presents a genetic predisposition her ovaries will contain more than
2 million little follicles each containing one immature egg. At puberty (~ 12 years old), most of these eggs will be absorbed and allowed to perish depleting the cohort of the ovarian reserve to approximately 350-400 thousand.
On each month it is estimated that 1000 follicles are lost through a process known as atresia while a single follicle
or sometimes two will reach final maturation and release one egg each. This loss of eggs is neither dependent on
the lifestyle one opts to pursue nor is limited to any hormone production, nutritional supplements or the administration
of an oral contraceptive pill.
The most common types of antibodies which
form with an elevated NK cell count are:
1. Anti-phospholipid antibodies 2. Antithyroid antibodies 3. Anti ovarian antibodies.
What is of the essence when investigating the presence of NK cells and especially the CD69 type subgroup in females with a history of early pregnancy loss or failure to conceive, is to affirm what triggered the elevated count. It must be appreciated that the human white blood cell membrane protein CD69 is an early activation marker induced not only by the NK cells but also by T lymphocytes and B cells (the major cellular components of the adaptive immune response) in response to any inflammatory stimuli. In this respect, an elevated CD69 marker may not be a result of a hyperactive NK cell population. It is well documented that elevated counts of the CD69 marker during peripheral blood assessment may not predict an autoimmune-related response by contrast an endometrial biopsy is a more useful diagnostic tool for establishing potential involvement of NK cells.
The second type of immune response can be encountered when a female raises antibodies in her cervical mucus creating a hostile environment for sperm survival following ejaculation. In essence, anti-sperm antibodies are an immune response raised by the female where specialised white blood cells attack the sperm impairing successful passage into the uterus through the cervix leading to compromised fertility.
Female infertility can result due to one or more
of the following reasons:
- Genetic (Chromosomal and/or gene defects)
- Endocrine (hormonal)
- Mechanical and Immunological
It is a fact that fertility in the female declines with advancing age and this phenomenon is attributed to two main reasons;
(a) the depletion of the ovarian reserve and (b) the fragility of the chromosomal complex of the existing egg cohort. A couple is advised to visit a specialist for an initial consultation and assessment after failure to conceive following 13 months of regular unprotected intercourse when the female spouse is up to 34 years of age while this period is reduced to 6 months when the age is 35 or more. Over 40 the chances become substantially slimmer and eminent advice should be sought.
The prevalence of chromosomal aberrations in an embryo is almost always a consequence of maternal age. This is because a female is born with the full complement of her eggs and this number will only decline over the years, unlike the human male where the dynamic process of spermatogenesis produces new spermatozoa continuously. In the process of their final maturation, both immature eggs and sperm follow a series of cellular divisions known as mitosis and meiosis. Successful fertilisation can only be achieved through the interaction of mature gametes.
Chromosome abnormalities typically occur as a result of errors during these cellular divisions although environmental exposure may also be an associating factor. Derangements in the normal process of these cellular divisions result in the egg acquiring or losing one or more chromosomes and therefore its genetic contribution at fertilisation will cause an imbalance resulting into early embryonic senescence or a miscarriage or the birth of a defective offspring (i.e. Dawn’s Syndrome). Similar aberrations but to a much lesser extent may be the consequence of abnormal cellular divisions post-fertilization (de novo) tampering the chromosomal complement of an early developing embryo in the uterus.
While nature most often detects the chromosomal imbalance and terminates the progress of the embryo at an early stage, at times the impaired embryo may develop into an abnormal birth. The advances in laboratory medicine today allow for investigating the chromosomal constitution of embryos created in vitro, therefore, enabling the replacement of those with only a healthy status.