Neither sex contributes more heavily than the other to infertility problems. Roughly one‑third of all infertile couples can trace their infertility to the woman, one‑third to the man, and one‑third to both partners. In practice this means that in >50% of cases there is both a male and a female factor involved. Understanding this reality before embarking on a strategic plan of treatment is in my opinion essential to optimizing outcome.
- Organic Pelvic Disease: The most common cause in a woman is damaged or blocked fallopian tubes that prevent the egg and sperm from uniting. Sexually transmitted diseases such as Chlamydia and Gonorrhea are a major cause of tubal scarring and blockage. In addition, scar tissue that forms after pelvic surgery may also lead to fertility problems. Conditions such as endometriosis, in which the lining of the uterus grows outside the womb (causing scarring, pain, and heavy bleeding), can also damage the fallopian tubes and ovaries. The presence of even a minimal amount of endometriosis in the pelvis is believed to adversely affect fertility by releasing toxic substances that might reduce the potential of the egg to be fertilized. The egg, of course, passes from the ovary through this environment to the fallopian tube, so while the presence of minimal endometriosis might not necessarily adversely affect the transportation mechanism, the exposure of eggs to this toxic environment diminishes its ability to become fertilized. It has also been shown that even the mildest form of endometriosis releases “toxins” into the local; pelvic environment. This can damage the woman’s eggs as they pass from the ovary(ies) with ovulation to the Fallopian tube(s) where the sperm are waiting. Once exposed to such “toxins” the envelopment of the egg (zona pellucida) becomes resistant to fertilization. This explains why all women with endometriosis (regardless of its severity) have markedly reduced fertility potential.
- Anatomical Ovarian Disease: Damaged ovaries may also contribute to infertility. Diseases such as chronic pelvic inflammatory disease, pelvic tuberculosis (mainly seen in Asia and Africa) advanced endometriosis, as well as post-surgically scarring, can compromise blood flow to the ovaries or directly destroy egg bearing ovarian tissue. It can also anchor the ovaries to surrounding pelvic structures , binding them down in an awkward position or creating a barrier that prevents the finger like extremities of the fallopian tubes (fimbriae) from applying themselves properly to the ovaries’ surface, thereby compromising “pick up” the egg at the time of ovulation.
- Ovulation dysfunction; One of the reasons that normal fertility usually wanes after 35 is because ovulation is more likely to become abnormal later in the childbearing years. Dysfunctional or absent ovulation is a frequent cause of female infertility. Some women do not ovulate at all, while others ovulate too early or too late in their cycle for a pregnancy to occur and survive. The older the woman and the closer she gets to menopause the greater the likelihood of hormonal dysfunction, irregular or absent ovulation. Such hormonal dysfunction can also occur independent of advancing age or proximity to menopause. Examples include hypothalamic anovulation, luteal and follicular phase insufficiency. Of course ovulation ceases with the onset of the menopause. It follow s that detection of irregular/absent menstruation or dysfunctional ovulation requires that ovarian reserve (AMH/FSH/LH/E2/) be tested and that future treatment be tailored accordingly.
- Egg quality/”competency”: The “competency”/quality of eggs inevitably declines progressively as women age beyond the early 30’s. This is largely because the older the woman, the more compromised egg maturation (Meiosis/maturational division/) which takes place 36-42 hours prior to ovulation, becomes. As a result the percentage of eggs that are chromosomally normal declines from around 1: 2 (in the early thirties) to about 1: 20 by the time the woman reaches 45y of age. Such chromosomally irregular eggs (aneuploid) are less likely to fertilize, develop normally, implant successfully or propagate a viable pregnancy. This is why the older the woman becomes, the lower her fertility potential, the higher the risk of miscarriage and the greater the chance of birth defects due to numerical chromosomal irregularities (e.g. Down syndrome).
- The uterine factor: A woman may also be infertile because disease, surgery, or infection has damaged the lining of her uterus. Damage caused by scarring or the presence of tumors, such as fibroids, may prevent the embryo from attaching to the endometrium and developing properly. Abnormalities in the size and shape of the uterus can also cause infertility problems. Sometimes women are born with an abnormally shaped uterus (congenital anomaly), but while this can cause mid-trimester miscarriages and premature birth, it rarely causes infertility. It is thus in my opinion inadvisable to remove a moderately severe uterine septum detected in the course or a routine assessment for infertility. Such practice can in my opinion lead to uterine scarring, and do more harm than good. Sometimes infertility is due to non-receptivity of the uterine lining (endometrium) to the embryo (fertilized and divided egg). This can be due be the lining being too thin to accommodate the implanting root system of the embryo, scarring of the lining, infection or immunologic factors. The latter is fast becoming an important consideration, especially in cases of unexplained failure following the use of fertility drugs.
- The cervical mucus factor: Some women are unable to produce good quality estrogen-induced cervical mucus, required for vitalization of sperm passing through the cervical canal during natural conception. The production of hostile cervical mucus might be due to infection or due to anti-sperm antibodies or an allergic response to their partner’s sperm. Sperm antibodies may be passed into the cervical secretions and thereby prevent fertilization by destroying or immobilizing the sperm. Occasionally, surgery or injury to the cervix may have destroyed the glands that produce cervical secretions.
- Immunologic Implantation Dysfunction: Some women develop antibodies to components of their own cells. This “autoimmune” process involves the production of antiphospholipid, antithyroid, and/or anti-ovarian antibodies – all of which may be associated with activation of Natural Killer (NK) cells in the uterine lining. Activated NK cells (NKa) release certain cytokines (TH-I) that if present in excess, often damage the trophoblast (the embryo’s root system) resulting in immunologic implantation dysfunction (IID). This can manifest as “infertility” or as early miscarriages). In other cases (though less common), the problem is due to “alloimmune” dysfunction. Here the genetic contribution by the male partner renders the embryo “too similar” to the mother. This in turn activates NK cells leading to implantation dysfunction. These IID’s are treated using combinations of medications such as heparin, Clexane, Lovenox, corticosteroids and intralipid (IL).
- Hormonal dysfunction: As with women, abnormal central hypothalamic-pituitary regulation can lead to poor gamete production. There are many factors that play a role in normal testicular production but the predominant influence on testicular sperm and hormonal production is regulated by pituitary LH and FSH. FSH impacts spermatogenesis predominantly and LH, male hormone production. Pituitary LH and FSH production and release is under the influence of hypothalamic regulation. As in women, so also with men, numerous factors ranging from environmental and stress-related issues; drugs; hormonal supplementation (e.g. use of male hormones to treat low-testosterone effects in men), intracranial trauma and tumors and a variety of diseases, can influence regulation of LH and FSH production/release and so can influence male fertility profoundly. In other cases, testicular failure can affect sperm production directly. This can result from radiation; surgery; chemotherapy, etc. It can also result from undescended testes at birth. The testicles should have descended into the scrotum shortly after birth, but in some cases they do not reach the scrotum for years. In such circumstances it may be necessary to accomplish this surgically when the man is very young to prevent the testicles from becoming severely damaged, thereby resulting in infertility
- Anatomical causes: The causes of male infertility are often more difficult to define. Blockage of the sperm ducts is one obvious cause. Generalized blockage may be caused by congenital absence of the sperm collecting ducts (vasa deferentia), from sexually transmitted diseases such as chlamydia or gonorrhea inflammation; trauma or from a prior vasectomy, done to effect male contraception. While it is usually possible to surgically reconnect the tubes after vasectomy, some men, especially those who underwent the procedure more than 10 years earlier, remain infertile because in the interim their systems have developed an immune reaction that results in the production of antibodies that destroy or immobilize their own sperm. Another common anatomical cause of male infertility is a varicocele, a collection of dilated veins around the testicles that hinders sperm function by increasing body temperature in the scrotum. In order for the testicles to produce healthy sperm, the temperature in the scrotum must be lower than it is in the rest of the body.
For about 10% of all infertile couples, the cause of the infertility cannot be readily determined by conventional diagnostic procedures. Such cases are referred to as “unexplained infertility.” Modern IVF technology is making great strides in helping to identify some of the causes of so called unexplained infertility. Improved testing techniques have made infertility easier to diagnose, and the majority of cases can now be diagnosed and generally are treatable. For example, recent research has demonstrated that many women with unexplained infertility ultimately are subsequently found to have pelvic endometriosis that cannot yet be detected by direct vision during laparoscopy or surgery. For example, a condition called non-pigmented endometriosis, in which the endometrium may be growing inside the pelvic cavity with many of the same deleterious effects as overt endometriosis, cannot be detected by direct vision because no visible bleeding has occurred in these lesions. The fertility of these patients may be every bit as much compromised by these conditions as if they had detectable endometriosis. Sometimes infertility is due to non-receptivity of the uterine lining (endometrium) to the embryo (fertilized and divided egg). This can be due be the lining being too thin to accommodate the implanting root system of the embryo, scarring of the lining, infection or immunologic factors. The latter is fast becoming an important consideration, especially in cases of unexplained failure following the use of fertility drugs.